Podcasts about borlaug

In every generation, important people predict that the end is near and the apocalypse is coming. In the 1960s, the fear was that population growth would destroy the planet—that fertility would outrun the food supply, and hundreds of millions of people would starve to death. The most famous warning was 'The Population Bomb,' a bestselling book published in 1968 by Stanford ecologist Paul Ehrlich, which claimed "the battle to feed all of humanity is over" and “hundreds of millions of people would starve to death” in the 1970s. But then the 1970s came and went. And global famine deaths didn't rise. They declined by 90 percent. In the 1980s, deaths from world hunger fell again. And again in the 1990s. And again in the 2000s. The apocalypse that everybody said was coming never came. And the reason is, basically, we invented super wheat. In the 1950s and 1960s, a plant pathologist named Norman Borlaug, working in Mexico on fungus-resistant wheat on a grant from the Rockefeller Foundation, managed to create a breed of wheat that was super abundant, efficient, and disease-resistant. His work kickstarted what's known as the Green Revolution, a movement whose discoveries are responsible for keeping roughly half the planet alive. In 2007, when Borlaug was 93, The Wall Street Journal editorialized that he had “arguably saved more lives than anyone in history. Maybe one billion.” Today's guest is Charles C. Mann, a journalist and author. We talk about the long history of the Green Revolution. Who was Norman Borlaug? What did he actually do? How did he do it? What does his accomplishment teach us about science, invention, and progress? We're at a moment today when American science is being cut to the bone while foreign aid is being slashed. I sometimes hear the question: What is foreign aid really worth to us? I think it's important to remember that Norman Borlaug was a foundation-funded scientist who didn't do his most important work in air-conditioned labs at Harvard or Johns Hopkins. His breakthroughs came in lean-to shacks in Mexico, where he worked to improve harvests. Without Borlaug's accomplishments, the world would look very different: Famines might trigger migration that destabilizes countries and transforms global politics. The world we have today, where countries like China and India can easily feed their huge populations, is a gift to global stability, to humanity, to America. It grew from the seed of a foreign agricultural support program. If you have questions, observations, or ideas for future episodes, email us at PlainEnglish@Spotify.com. Host: Derek Thompson Guest: Charles C. Mann Producer: Devon Baroldi Learn more about your ad choices. Visit podcastchoices.com/adchoices

Norman Borlaug est sans doute l'un des héros les plus méconnus du XXe siècle. Cet agronome américain, né en 1914 dans l'Iowa, est considéré comme le père de la « Révolution verte », un mouvement qui a transformé l'agriculture mondiale et permis de lutter efficacement contre la famine dans de nombreux pays en développement. Grâce à ses travaux, on estime qu'il aurait sauvé plus d'un milliard de personnes de la sous-alimentation.Après des études en biologie et phytopathologie, Borlaug entame sa carrière au Mexique dans les années 1940, dans le cadre d'un programme financé par la Fondation Rockefeller. À cette époque, le pays fait face à des rendements agricoles très faibles et à des maladies du blé comme la rouille. C'est dans ce contexte qu'il commence à développer des variétés de blé naines, à haut rendement et résistantes aux maladies, capables de pousser dans des conditions climatiques difficiles.Ces nouvelles variétés s'accompagnent d'un ensemble de techniques agricoles modernisées : irrigation contrôlée, engrais chimiques, pesticides et sélection génétique. Cette combinaison, qui sera plus tard appelée Révolution verte, est ensuite appliquée à d'autres cultures, notamment le riz et le maïs. En quelques années, la production de blé au Mexique double, et le pays devient auto-suffisant en céréales dès 1956.Le succès mexicain attire l'attention d'autres nations. Dans les années 1960, l'Inde et le Pakistan, alors menacés par la famine, adoptent les méthodes de Borlaug. En très peu de temps, la production céréalière y explose : l'Inde passe d'importatrice à exportatrice de blé en moins d'une décennie. Ce tournant spectaculaire permet de nourrir des millions de personnes, dans un contexte de croissance démographique galopante.Pour cet accomplissement exceptionnel, Norman Borlaug reçoit en 1970 le prix Nobel de la paix, une distinction rarement accordée à un scientifique. Le comité Nobel souligne que « plus que toute autre personne de son époque, il a contribué à assurer la paix dans le monde en réduisant la faim ».Cependant, la Révolution verte n'est pas exempte de critiques. Certains soulignent l'impact écologique de l'agriculture intensive : épuisement des sols, usage massif de produits chimiques, réduction de la biodiversité. D'autres pointent des inégalités sociales, les petits agriculteurs n'ayant pas toujours les moyens d'accéder à ces technologies.Malgré ces limites, l'œuvre de Borlaug reste monumentale. Jusqu'à sa mort en 2009, il n'a cessé de défendre l'importance de la science pour nourrir l'humanité. Son héritage demeure une source d'inspiration pour les chercheurs du XXIe siècle face aux défis de la sécurité alimentaire mondiale. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

In the 1960s, a deep anxiety set in as one thing became seemingly clear: We were headed toward population catastrophe. Paul Ehrlich's “The Population Bomb” and “The Limits to Growth,” written by the Club of Rome, were just two publications warning of impending starvation due to simply too many humans on the earth.As the population ballooned year by year, it would simply be impossible to feed everyone. Demographers and environmentalists alike held their breath and braced for impact.Except that we didn't starve. On the contrary, we were better fed than ever.In his article in The New Atlantis, Charles C. Mann explains that agricultural innovation — from improved fertilization and irrigation to genetic modification — has brought global hunger to a record low.Today on Faster, Please! — The Podcast, I chat with Mann about the agricultural history they didn't teach you in school.Mann is a science journalist who has worked as a correspondent for The Atlantic, Science, and Wired magazines, and whose work has been featured in many other major publications. He is also the author of 1491: New Revelations of the Americas Before Columbus and1493: Uncovering the New World Columbus Created, as well as The Wizard and the Prophet: Two Remarkable Scientists and Their Dueling Visions to Shape Tomorrow's World.In This Episode* Intro to the Agricultural Revolution (2:04)* Water infrastructure (13:11)* Feeding the masses (18:20)* Indigenous America (25:20)Below is a lightly edited transcript of our conversation. Intro to the Agricultural Revolution (2:04)I don't think that people realize that the fact that most people on earth, almost the average person on earth, can feed themselves is a novel phenomenon. It's something that basically wasn't true since as far back as we know.Pethokoukis: What got my attention was a couple of pieces that you've worked on for The New Atlantis magazine looking at the issue of how modern Americans take for granted the remarkable systems and infrastructure that provide us comfort, safety, and a sense of luxury that would've been utterly unimaginable even to the wealthiest people of a hundred years ago or 200 years ago.Let me start off by asking you: Does it matter that we do take that for granted and that we also kind of don't understand how our world works?Mann: I would say yes, very much. It matters because these systems undergird the prosperity that we have, the good fortune that we have to be alive now, but they're always one generation away from collapse. If they aren't maintained, upgraded and modernized, they'll fall apart. They just won't stand there. So we have to be aware of this. We have to keep our eye on the ball, otherwise we won't have these things.The second thing is that, if we don't know how our society works, as citizens, we're simply not going to make very good choices about what to do with that society. I feel like both sides in our current political divide are kind of taking their eye off the ball. It's important to have good roads, it's important to have clean water, it's important to have a functioning public health system, it's important to have an agricultural system that works. It doesn't really matter who you are. And if we don't keep these things going, life will be unnecessarily bad for a lot of people, and that's just crazy to do.Is this a more recent phenomenon? If I would've asked people 50 years ago, “Explain to me how our infrastructure functions, how we get water, how we get electricity,” would they have a better idea? Is it just because things are more complicated today that we have no idea how our food gets here or why when we turn the faucet, clean water comes out?The answer is “yes” in a sort of trivial sense, in that many more people were involved in producing food, a much greater percentage of the population was involved in producing food 50 years ago. The same thing was true for the people who were building infrastructure 50 years ago.But I also think it's generally true that people's parents saw the change and knew it. So that is very much the case and, in a sense, I think we're victims of our own success. These kinds of things have brought us so much prosperity that we can afford to do crazy things like become YouTube influencers, or podcasters, or freelance writers. You don't really have any connection with how the society goes because we're sort of surfing on this wave of luxury that our ancestors bequeathed to us.I don't know how much time you spend on social media, Charles — I'm sure I spend too much — but I certainly sense that many people today, younger people especially, don't have a sense of how someone lived 50 years ago, 100 years ago, and there was just a lot more physical suffering. And certainly, if you go back far enough, you could not take for granted that you would have tomatoes in your supermarket year round, that you would have water in the house and that water would be clean. What I found really interesting — you did a piece on food and a piece on water — in the food piece you note that, in the 1980s, that was a real turning point that the average person on earth had enough to eat all the time, and rather than becoming an issue of food production, it became an issue of distribution, of governance. I think most people would be surprised of that statistic even though it's 40 years old.I don't think that people realize that the fact that most people on earth, almost the average person on earth, can feed themselves is a novel phenomenon. It's something that basically wasn't true since as far back as we know. That's this enormous turning point, and there are many of these turning points. Obviously, the introduction of antibiotics for . . . public health, which is another one of these articles they're going to be working on . . .Just about 100 years ago today, when President Coolidge was [president], his son went to play tennis at the White House tennis courts, and because he was lazy, or it was fashionable, or something, he didn't put on socks. He got a blister on his toe, the toe got infected, and he died. 100 years ago, the president of the United States, who presumably had the best healthcare available to anybody in the world, was unable to save his beloved son when the son got a trivial blister that got infected. The change from that to now is mind boggling.You've written about the Agricultural Revolution and why the great fears 40 or 50 years ago of mass starvation didn't happen. I find that an endlessly interesting topic, both for its importance and for the fact it just seems to be so underappreciated to this day, even when it was sort of obvious to people who pay attention that something was happening, it still seemed not to penetrate the public consciousness. I wonder if you could just briefly talk to me about that revolution and how it happened.The question is, how did it go from “The Population Bomb” written in 1968, a huge bestseller, hugely influential, predicting that there is going to be hundreds of millions of people dying of mass starvation, followed by other equally impassioned, equally important warnings. There's one called “Famine, 1975!,” written a few years before, that predicted mass famines in 1975. There's “The Limits to Growth.” I went to college in the '70s and these were books that were on the curriculum, and they were regarded as contemporary classics, and they all proved to be wrong.The reason is that, although they were quite correct about the fact that the human race was reproducing at that time faster than ever before, they didn't realize two things: The first is that as societies get more affluent, and particularly as societies get more affluent and give women more opportunities, birth rates decline. So that this was obviously, if you looked at history, going to be a temporary phenomenon of whatever length it was be, but it was not going to be infinite.The second was there was this enormous effort spurred by this guy named Norman Borlaug, but with tons of other people involved, to take modern science and apply it to agriculture, and that included these sort of three waves of innovation. Now, most innovation is actually just doing older technologies better, which is a huge source of progress, and the first one was irrigation. Irrigation has been around since forever. It's almost always been done badly. It's almost always not been done systematically. People started doing it better. They still have a lot of problems with it, but it's way better, and now 40 percent, roughly, of the crops in the world that are produced are produced by irrigation.The second is the introduction of fertilizer. There's two German scientists, Fritz Haber and Carl Bosch, who essentially developed the ways of taking fertilizer and making lots and lots of it in factories. I could go into more detail if you want, but that's the essential thing. This had never been done before, and suddenly cheap industrial fertilizer became available all over the world, and Vaclav Smil . . . he's sort of an environmental scientist of every sort, in Manitoba has calculated that roughly 40 percent of the people on earth today would not be alive if it wasn't for that.And then the third was the development of much better, much higher-yielding seeds, and that was the part that Norman Borlaug had done. These packaged together of irrigation fertilizer and seeds yielded what's been called the Green Revolution, doubled, tripled, or even quadrupled grain yields across the world, particularly with wheat and rice. The result is the world we live in today. When I was growing up, when you were growing up, your parents may have said to you, as they did me, Oh, eat your vegetables, there are kids that are starving in Asia.” Right? That was what was told and that was the story that was told in books like “The Population Bomb,” and now Asia's our commercial rival. When you go to Bangkok, that was a place that was hungry and now it's gleaming skyscrapers and so forth. It's all based on this fact that people are able to feed themselves through the combination of these three factors,That story, the story of mass-starvation that the Green Revolution irrigation prevented from coming true. I think a surprising number of people still think that story is relevant today, just as some people still think the population will be exploding when it seems clear it probably will not be exploding. It will rise, but then it's going to start coming down at some point this century. I think those messages just don't get through. Just like most people don't know Norm Borlaug, the Haber-Bosch process, which school kids should know. They don't know any of this. . . Borlaug won the Nobel Prize, right?Right. He won the Nobel Peace Prize. I'll tell you a funny story —I think he won it in the same year that “The Population Bomb” came out.It was just a couple years off. But you're right, the central point is right, and the funny thing is . . . I wrote another book a while back that talked about this and about the way environmentalists think about the world, and it's called the “Wizard and the Prophet” and Borlaug was the wizard of it. I thought, when I proposed it, that it would be easy. He was such an important guy, there'd be tons of biographies about him. And to this day, there isn't a real serious scholarly biography of the guy. This is a person who has done arguably more to change human life than any other person in the 20th century, certainly up in the top dozen or so. There's not a single serious biography of him.How can that be?It's because we're tremendously disconnected. It's a symptom of what I'm talking about. We're tremendously disconnected from these systems, and it's too bad because they're interesting! They're actually quite interesting to figure out: How do you get water to eight billion people? How do you get . . . It is a huge challenge, and some of the smartest people you've ever met are working on it every day, but they're working on it over here, and the public attention is over here.Water infrastructure (13:11). . . the lack of decent, clean, fresh water is the world's worst immediate environmental problem. I think people probably have some vague idea about agriculture, the Agricultural Revolution, how farming has changed, but I think, as you just referred to, the second half, water — utter mystery to people. Comes out of a pipe. The challenges of doing that in a rich country are hard. The challenges doing a country not so rich, also hard. Tell me what you find interesting about that topic.Well, whereas the story about agriculture is basically a good story: We've gotten better at it. We have a whole bunch of technical innovations that came in the 20th century and humankind is better off than ever before. With water, too, we are better off than ever before, but the maddening thing is we could be really well off because the technology is basically extremely old.There's a city, a very ancient city called Mohenjo-daro that I write about a bit in this article that was in essentially on the Pakistan-India border, 2600 BC. And they had a fully functioning water system that, in its basics, was no different than the water system that we have, or that London has, or that Paris has. So this is an ancient, ancient technology, yet we still have two billion people on the planet that don't have access to adequate water. In fact, even though we know how to do it, the lack of decent, clean, fresh water is the world's worst immediate environmental problem. And a small thing that makes me nuts is that climate change — which is real and important — gets a lot of attention, but there are people dying of not getting good water now.On top of it, even in rich countries like us, our water system is antiquated. The great bulk of it was built in the '40s, '50s, and '60s, and, like any kind of physical system, it ages, and every couple years, various engineering bodies, water bodies, the EPA, and so forth puts out a report saying, “Hey, we really have to fix the US water system and the numbers keep mounting up.” And Democrats, Republicans, they all ignore this.Who is working on the water issue in poorer countries?There you have a very ad hoc group of people. The answer is part of it's the Food and Agricultural Organization because most water in most countries is used for irrigation to grow food. You also have the World Health Organization, these kinds of bodies. You have NGOs working on it. What you don't have in those countries like our country is the government taking responsibility for coordinating something that's obviously in the national interest.So you have these things where, very periodically — a government like China has done this, Jordan has done this, Bolivia has done this, countries all over the world have done this — and they say, “Okay, we haven't been able to provide freshwater. Let's bring in a private company.” And the private company then invests all this money in infrastructure, which is expensive. Then, because it's a private company, it has to make that money back, and so it charges people for a lot of money for this, and the people are very unhappy because suddenly they're paying a quarter of their income for water, which is what I saw in Southwest China: water riots because people are paying so much for water.In other words, one of the things that government can do is sort of spread these costs over everybody, but instead they concentrate it on the users, Almost universally, these privatization efforts have led to tremendous political unhappiness because the government has essentially shifted responsibility for coordinating and doing these things and imposed a cost on a narrow minority of the users.Are we finally getting on top of the old water infrastructure in this country? It seems like during the Biden administration they had a big infrastructure bill. Do you happen to know if we are finally getting that system upgraded?Listen, I will be the only person who probably ever interviews you who's actually had to fix a water main as a summer job. I spent [it at] my local Public Works Department where we'd have to fix water mains, and this was a number of years ago, and even a number of years ago, those pipes were really, really old. It didn't take much for them to get a main break.I'm one of those weird people who is bothered by this. All I can tell you is we have a lot of aging infrastructure. The last estimate that I've seen came before this sort of sudden jerky rise of construction costs, which, if you're at all involved in building, is basically all the people in the construction industry talk about. At that point, the estimate was that it was $1.2 trillion to fix the infrastructure that we have in the United States. I am sure it is higher now. I am delighted that the Biden people passed this infrastructure — would've been great if they passed permitting reform and a couple of other things to make it easier to spend the money, but okay. I would like to believe that the Trump people would take up the baton and go on this.Feeding the masses (18:20)I do worry that the kind of regulations, and rules, and ideas that we put into place to try and make agriculture more like this picture that we have in our head will end up inadvertently causing suffering for the people who are struggling.We're still going to have another two billion people, maybe, on this earth. Are we going to be able to feed them all?Yeah, I think that there's no question. The question is what we're going to be able to feed them? Are we going to be able to feed them all, filet mignon and truffled . . . whatever they put truffle oil on, and all that? Not so sure about that.All organic vegetables.At the moment, that seems really implausible, and there's a sort of fundamental argument going on here. There's a lot of people, again, both right and left, who are sort of freaked out by the scale that modern agriculture operates on. You fly over the middle-west and you see all those circles of center-pivot irrigation, they plowed under, in the beginning of the 20th century, 100 million acres of prairie to produce all that. And it's done with enormous amounts of capital, and it was done also partly by moving people out so that you could have this enormous stuff. The result is it creates a system that . . . doesn't match many people's vision of the friendly family farmer that they grew up with. It's a giant industrial process and people are freaked out by the scale. They don't trust these entities, the Cargills and the ADMs, and all these huge companies that they see as not having their interests at heart.It's very understandable. I live in a small town, we have a farm down there, and Jeremy runs it, and I'm very happy to see Jeremy. There's no Jeremy at Archer Daniels Midland. So the result is that there's a big revulsion against that, and people want to downsize the scale, and they point to very real environmental problems that big agriculture has, and they say that that is reason for this. The great problem is that in every single study that I am aware of, the sort of small, local farms don't produce as much food per acre or per hectare as the big, soulless industrial processes. So if you're concerned about feeding everybody, that's something you have to really weigh in your head, or heavy in your heart.That sort of notion of what a farm should look like and what good food is, that kind of almost romantic notion really, to me, plays into the sort of anti-growth or the degrowth people who seemed to be saying that farms could only be this one thing — probably they don't even remember those farms anymore — that I saw in a storybook. It's like a family farm, everything's grown local, not a very industrial process, but you're talking about a very different world. Maybe that's a world they want, but I don't know if that's a world you want if you're a poor person in this world.No, and like I said, I love going to the small farm next to us and talking to Jeremy and he says, “Oh look, we've just got these tomatoes,” it's great, but I have to pay for that privilege. And it is a privilege because Jeremy is barely making it and charging twice as much as the supermarket. There's no economies of scale for him. He still has to buy all the equipment, but he's putting it over 20 acres instead of 2000 acres. In addition, it's because it's this hyper-diverse farm — which is wonderful; they get to see the strawberries, and the tomatoes, and all the different things — it means he has to hire much more labor than it would be if he was just specializing in one thing. So his costs are inevitably much, much higher, and, therefore, I have to pay a lot more to keep him going. That's fine for me; I'm a middle-class person, I like food, this can be my hobby going there.I'd hate to have somebody tell me it's bad, but it's not a system that is geared for people who are struggling. There are just a ton of people all over the world who are struggling. They're better off than they were 100 years ago, but they're still struggling. I do worry that the kind of regulations, and rules, and ideas that we put into place to try and make agriculture more like this picture that we have in our head will end up inadvertently causing suffering for the people who are struggling.To make sure everybody can get fed in the future, do we need a lot more innovation?Innovation is always good. I would say that we do, and the kinds of innovation we need are not often what people imagine. For example, it's pretty clear that parts of the world are getting drier, and therefore irrigation is getting more difficult. The American Southwest is a primary candidate, and you go to the Safford Valley, which I did a few years ago — the Safford Valley is in southeast Arizona and it's hotter than hell there. I went there and it's 106 degrees and there's water from the Colorado River, 800 miles away, being channeled there, and they're growing Pima cotton. Pima cotton is this very good fine cotton that they use to make fancy clothes, and it's a great cash crop for farmers, but growing it involves channeling water from the Colorado 800 miles, and then they grow it by what's called flood irrigation, which is where you just fill the field with an inch of water. I was there actually to see an archeologist who's a water engineer, and I said to him, “Gee, it's hot! How much that water is evaporated?” And he said, “Oh, all of it.”So we need to think about that kind of thing if the Colorado is going to run out of water, which it is now. There's ways you can do it, you can possibly genetically modify cotton to use less water. You could drip irrigation, which is a much more efficient form of irrigation, it's readily available, but it's expensive. So you could try to help farmers do that. I think if you cut the soft costs, which is called the regulatory costs of farming, you might be able to pay for it in that way. That would be one type of innovation. Another type of thing you could do is to do a different kind of farming which is called civil pastoral systems, where you grow tree crops and then you grow cattle underneath, and that uses dramatically less water. It's being done in Sonora, just across the border and the tree crops — trees are basically wild. People don't breed them because it takes so long, but we now have the tools to breed them, and so you could make highly productive trees with cattle underneath and have a system that produces a lot of calories or a lot of good stuff. That's all the different kinds of innovation that we could do. Just some of the different kinds of innovation we could do and all would help.Indigenous America (25:20)Part of the reason I wrote these things is that I realized it's really interesting and I didn't learn anything about it in school.Great articles in The New Atlantis, big fan of “Wizard and the Prophet,” but I'm going to take one minute and ask you about your great books talking about the story of the indigenous peoples of the Americas. If I just want to travel in the United States and I'm interested in finding out more about Native Americans in the United States, where would you tell me to go?One of my favorite places just it's so amazing, is Chaco Canyon, and that's in the Four Corners area — that whole Four Corners area is quite incredible — and Chaco Canyon is a sign that native people could build amazing stuff, and native people could be crazy, in my opinion. It's in the middle of nowhere, it has no water, and for reasons that are probably spiritual and religious, they built an enormous number of essentially castles in this canyon, and they're incredible.The biggest one, Pueblo Bonito as it's called now, it's like 800 rooms. They're just enormous. And you can go there, and you can see these places, and you can just walk around, and it is incredible. You drive up a little bit to Mesa Verde and there's hundreds of these incredible cliff dwellings. What seems to have happened — I'm going to put this really informally and kind of jokingly to you, not the way that an archeologist would talk about it or I would write about it, but what looks like it happened is that the Chaco Canyon is this big canyon, and on the good side that gets the southern exposure is all these big houses. And then the minions and the hoi polloi lived on the other side, and it looks like, around 800, 900, they just got really tired of serving the kings and they had something like a democratic revolution, and they just left, most of them, and founded the Pueblos, which is these intensely democratic self-governing bodies that are kind of like what Thomas Jefferson thought the United States should be.Then it's like all the doctors, and the lawyers, and the MBAs, and the rich guys went up to Mesa Verde and they started off their own little kingdoms and they all fought with each other. So you have these crazy cliff dwellings where it's impossible to get in and there's hundreds of people living in these niches in these cliffs, and then that blew up too. So you could see history, democracy, and really great architecture all in one place.If someone asked me for my advice about changing the curriculum in school, one, people would leave school knowing who the heroes of progress and heroes of the Agricultural Revolution were. And I think they'd also know a lot more about pre-Columbian history of the Americas. I think they should know about it but I also think it's just super interesting, though of course you've brought it to life in a beautiful way.Thank you very much, and I couldn't agree with you more. Part of the reason I wrote these things is that I realized it's really interesting and I didn't learn anything about it in school.On sale everywhere The Conservative Futurist: How To Create the Sci-Fi World We Were PromisedFaster, Please! is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. This is a public episode. 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In this episode, co-hosts Elliot Turner and John Mihaljevic welcome Jon aka Borlaug for a deep dive on the life science space, covering the bioprocessors, CRO/CDMOs, and the diagnostics companies. Jon helps demystify this fascinating industry for generalists and offers sharp insights for specialists alike. We go in depth on why life science companies have suffered post-COVID and how better days await. Jon shares why bioprocessing is one of the best business models in the world. Stay until the end when he shares his favorite bioprocessing idea.  For more on the space, follow Jon on Twitter https://x.com/Borlaug_ and sign up for his substack https://borlaug.substack.com Enjoy this conversation!   The primary purpose of this podcast is to educate and inform. The views, information, or opinions expressed by hosts or guests are their own. Neither this show, nor any of its content should be construed as investment advice or as a recommendation to buy or sell any particular security. Security specific information shared on this podcast should not be relied upon as a basis for your own investment decisions -- be sure to do your own research. The podcast hosts and participants may have a position in the securities mentioned, personally, through sub accounts and/or through separate funds and may change their holdings at any time.   About the Co-Hosts: Elliot Turner is a co-founder and Managing Partner, CIO at RGA Investment Advisors, LLC. RGA Investment Advisors runs a long-term, low turnover, growth at a reasonable price investment strategy seeking out global opportunities. Elliot focuses on discovering and analyzing long-term, high quality investment opportunities and strategic portfolio management. Prior to joining RGA, Elliot managed portfolios at at AustinWeston Asset Management LLC, Chimera Securities and T3 Capital. Elliot holds the Chartered Financial Analyst (CFA) designation as well as a Juris Doctor from Brooklyn Law School.. He also holds a Bachelor of Arts degree from Emory University where he double majored in Political Science and Philosophy. John Mihaljevic leads MOI Global and serves as managing editor of The Manual of Ideas. He managed a private partnership, Mihaljevic Partners LP, from 2005-2016. John is a winner of the Value Investors Club's prize for best investment idea. He is a trained capital allocator, having studied under Yale University Chief Investment Officer David Swensen and served as Research Assistant to Nobel Laureate James Tobin. John holds a BA in Economics, summa cum laude, from Yale and is a CFA charterholder.

Join CardioNerds Heart Failure Section Chair Dr. Jenna Skowronski, episode lead Dr. Merna Hussein, and expert faculty Dr. Milton Packer as they discuss the SUMMIT trial. The SUMMIT trial randomized 731 patients with HFpEF with LVEF ≥ 50% and obesity with BMI ≥ 30 kg/m2 to receive tirzepatide or placebo for at least 52 weeks. The two co-primary endpoints were a composite of time to cardiovascular death or a worsening heart failure event and quality of life measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Treatment with tirzepatide led to a lower risk of the composite of cardiovascular death or worsening heart failure as well as improved quality of life. This episode was planned in collaboration with the American College of Cardiology Section of the Prevention of Cardiovascular Disease with mentorship from Section Chair Dr. Eugenia Gianos. CardioNerds Journal Club PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! References - The SUMMIT Trial Packer, M., Zile, M. R., Kramer, C. M., Baum, S. J., Litwin, S. E., Menon, V., Ge, J., Weerakkody, G. J., Ou, Y., Bunck, M. C., Hurt, K. C., Murakami, M., Borlaug, B. A., & SUMMIT Trial Study Group. (2024). Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2410027

2024 World Food Prize laureates Cary Fowler and Geoffrey Hawtin were honored for their life work protecting crop biodiversity at the Borlaug International Dialogue. We asked Fowler about the creation of the Svalbard Global Seed Vault.Then, Jim Snee, CEO of Hormel, and his wife Tammy discuss Hormel's Hometown Food Security Project, and Manuel Otero, IICA director general, spoke on farmers' challenges to adopt new technology.Want to receive Newsmakers in your inbox every week? Sign up! http://eepurl.com/hTgSAD

In today's show Dustin is joined by Iowa Secretary of Agriculture Mike Naig to discuss Iowa ag being in the spotlight during the Borlaug discussion at the World Food Prize, Andy brings us a portion of the latest episode of Pods of Potential, and we have comments from Senator Chuck Grassley about the Pure Prairie Poultry situation.

1970 erhält ein amerikanischer Wissenschaftler den Friedensnobelpreis für seine Bemühungen zur "Verbesserung der Landwirtschaft". Als die mexikanische Regierung 1943 die Rockefeller Foundation zur Hilfe ruft, um den Pilzbefall der Weizenpflanzen zu investigieren, ist Borlaug mit seinem Team zur Stelle und das Unheil nimmt seinen Lauf...

Whoa, just went to the Normal Borlaug Boyhood Home in NE Iowa. If you are planning a trip to the Driftless Region, this should definitely be on your itinerary. I explain what you can expect, how you can plan, offer some tips and explain a little bit about the man, Norman Borlaug, the Elvis of wheat research. He is credited with saving over one billion lives through adoption of his farming methods and strains of wheat that it he developed. Experience what made hom great! Absolutely loved this trip to Normal Borlaug Boyhood Home!!

What does it mean to be the salt of the world? In this episode, we sit down with Erik Borlaug, evangelist at West End church of Christ and discuss the Christian's role in being the salt of the earth.

Komu można przypisać uratowanie największej liczby istnień ludzkich w historii? Być może nie ma bezpośredniej odpowiedzi na to pytanie, ale jedną osobą, której nazwisko zawsze się pojawia przy okazji tego pytania, jest Normal Borlaug. Borlaug został nazwany "zapomnianym dobroczyńcą ludzkości" i był laureatem Pokojowej Nagrody Nobla. Jego wysiłki w celu uratowania życia ponad miliarda ludzi zostały uznane właśnie tą nagrodą. Jednak niewiele osób wie, kim on jest. Poznaj inspirującą historię człowieka, który uratował świat w tym odcinku WszystkoWszędzie. To jest nowy podcast, bardzo potrzebuję :) Twojej pozytywnej recenzji na Spotify, Apple Podcasts czy Google Podcasts, albo na YouTube. Jeśli to co usłyszałeś lub usłyszałaś było ciekawe, poświęć minutkę na napisanie recenzji, to pomoże mi kontynuować tą historię i da motywację na dalsze odcinki. Codziennie. #podcast #słuchowisko #wszystkowszedzie #codziennie #wszystko #wszędzieSłuchamy na Spotify: https://open.spotify.com/show/5jAxA7ZCDIJ3c4oYIabP3k?si=49af7c981a164025Słuchamy na Apple Podcasts: https://podcasts.apple.com/nl/podcast/wszystkowszedzie/id1707180797Słuchamy na YouTube:https://youtube.com/@WszystkoWszedzie?si=XLuxsEXMonapvolg Oglądamy na Instagramiehttps://instagram.com/wszystkowszedzieplOglądamy na Facebookuhttps://www.facebook.com/wszystkowszedziepl/ Oglądamy na X dawniej Twitterhttps://twitter.com/WszystkoWszedziNasza strona www:https://wszystkowszedzie.buzzsprout.com

Wednesday's Second Hour: The 2023 Norman E. Borlaug International Dialogue is underway in Des Moines and David Geiger caught up with a couple of the participants. To start the hour, we hear a conversation he had with Former Governor of Iowa Terry Branstad about the inaugural World Food Prize and the past laureates. He also talks with representatives from the Norman Borlaug Heritage Foundation. At the end of the show we talk with Al Kluis of Kluis Commodity Advisors about markets, minutes after the announcement of an elected Speaker of the House of Representatives.

Today's podcast is titled, “Origins of The International Rice Research Institute.” Dr. Norman Borlaug, 1970 Nobel Peace Prize Winner, and Dr. Robert Chandler, Founding Director Emeritus of the International Rice Research Institute, discuss the origins of the International Rice Research Institute and describe how the impetus for the Institute began with Borlaug's work with wheat in Mexico. Recorded in 1994. Listen now, and don't forget to subscribe to get updates each week for the Free To Choose Media Podcast.

The Green Revolution was a program of agricultural technology transfer that helped poor countries around the world increase food production from the 1950s onward. An American agronomist named Norman Borlaug developed and popularized the central innovation of this revolution: the concept of “wide adaptation,” or the idea that plants could be bred to produce a high yield in a variety of environments, rather than in a particular region. Borlaug's work won him the Nobel Prize in 1970, and his agricultural insights are often credited with saving millions of people from hunger. But the legacy of Borlaug and the Green Revolution is not as straightforward as these accolades suggest.  In this episode, we caught up with interdisciplinary scientist and historian Marci Baranski to discuss her new book, The Globalization of Wheat: A Critical History of the Green Revolution. She talks with host Jason Lloyd about how a more nuanced understanding of the Green Revolution and Borlaug's work can improve agricultural and economic development policies today. Resources: Marci Baranski's book, The Globalization of Wheat: A Critical History of the Green Revolution Madhumita Saha's book review, “Left Behind by the Green Revolution” (Issues, Summer 2023) Marci Baranski and Mary Ollenberger's essay, “How to Improve the Social Benefits of Agricultural Research” (Issues, Spring 2020)

The 2 Andys discuss the impact of the Borlaug Scholarship, a program that provides financial support to students pursuing agricultural studies. Learn more about this important initiative. The post The 2 Andys Talks About the Value of the Borlaug Scholarship appeared first on Seed World.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Hugh Thompson Jr (1943–2006), published by Gavin on December 10, 2022 on The Effective Altruism Forum. On the 30th anniversary of the massacre, Thompson went back to My Lai and met some of the people whose lives he had saved. "One of the ladies that we had helped out that day came up to me and asked, ‘Why didn't the people who committed these acts come back with you?' And I was just devastated. And then she finished her sentence: she said, ‘So we could forgive them.' I'm not man enough to do that. I'm sorry. I wish I was, but I won't lie to anybody. I'm not that much of a man." Hugh Thompson was a volunteer officer in the Vietnam War who turned his squad's weapons on American soldiers to stop them raping and murdering more women and children than the four or five hundred they already had. He models the standard idea of heroism: one day, one decision, clarity, evil men to defy, faces you can see. Then, a system to navigate, betrayal, self-sacrifice, being punished for virtue. I'm writing about him because of how the story makes me feel. It is a fault of my feeling that I feel like this about Thompson and not Borlaug. One day Thompson and his crew, who at first thought the artillery bombardment caused all the civilian deaths on the ground, became aware that Americans were murdering the villagers after a wounded civilian woman they requested medical evacuation for, Nguyễn Thị Tẩu, was murdered right in front of them by Captain Medina, the commanding officer of the operation... "It was a Nazi kind of thing." Immediately realizing that the soldiers intended to murder the Vietnamese civilians, Thompson landed his helicopter between the advancing ground unit and the villagers. He turned to Colburn and Andreotta and ordered them to shoot the men in the 2nd Platoon if they attempted to kill any of the fleeing civilians... “Open up on ‘em. Blow ‘em away.” While Colburn and Andreotta trained their guns on the 2nd Platoon, Thompson located as many civilians as he could, persuaded them to follow him to a safer location, and ensured their evacuation... "Later that day, sometime in the afternoon, after they had gone through the village, we were back out there again. [The murderers] were just casually, nonchalantly sitting around around smoking and joking with their steel pots off just like nothing had happened. There were five or six hundred bodies less than a quarter of a mile from them. I just couldn't understand it." ...senior American Division officers cancelled similar planned operations by Task Force Barker against other villages... possibly preventing the additional massacre of further hundreds, if not thousands, of Vietnamese civilians. Synecdoche in the Vietnamese province of Quang Ngai, where the Mỹ Lai massacre occurred, up to 70% of all villages were destroyed by the air strikes and artillery bombardments, including the use of napalm; 40 percent of the population were refugees, and the overall civilian casualties were close to 50,000 a year... 203 U.S. personnel were charged with crimes, 57 of them were court-martialed and 23 of them were convicted. The VWCWG also investigated over 500 additional alleged atrocities but it could not verify them. [A draw: ] PFC Herbert L. Carter; shot himself in the foot while reloading his pistol and claimed that he shot himself in the foot in order to be MEDEVACed out of the village when the massacre started. Coverup Thompson quickly received the Distinguished Flying Cross for his actions at Mỹ Lai. The citation for the award fabricated events, for example praising Thompson for taking to a hospital a Vietnamese child "...caught in intense crossfire". It also stated that his "...sound judgment had greatly enhanced Vietnamese–American relations in the operational area". Thompson threw away the citation. Initial reports claimed "128 Viet C...

This week, please join authors Kevin Roedl and Sebastian Wolfrum, as well as Associate Editor Mark Link as they discuss the article "Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary, and backstage pass to the Journal and its editors. We are your cohosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor and Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, very interesting, a randomized clinical trial of temperature control after in-hospital cardiac arrest. But before we get to that exciting study, let's grab a cup of coffee, and jump in and discuss some of the other articles in the issue. Carolyn, would you like to go first? Dr. Carolyn Lam: Yes. Starting with a great quiz. So Greg, which is better? How about this? It's multiple choice. Is it A; transradial, or B; transfemoral access, in terms of post-procedural mortality? Dr. Greg Hundley: I'm going to go with transradial. It has been, hopefully, I'm okay on this. It just seems so many fewer complications. Dr. Carolyn Lam: But that's exactly that we need to meta-analyze the studies that have been done. Exactly what this paper did, led by Professor Valgimigli, from USI in Lugano, Switzerland. So what they did is, they performed an individual patient data meta-analysis of 21,600 patients, enrolled in seven multi-center randomized control trials, comparing the transradial with transfemoral access, among patients undergoing coronary angiography with or without PCI. And they found that transradial access was associated with a lower incidence of the primary outcome of all-cause mortality, and the co-primary outcome of major bleeding at 30 days, compared to transfemoral access. There was also evidence for reductions in major adverse cardiac and cerebral vascular events, net adverse clinical events, vascular complications, excess site bleeding, and blood transfusion. MI, stroke, and stent thrombosis, did not differ. And crossover was higher in the transradial access group. At predefined subgroup analysis, the authors confirmed that the benefit observed the transradial group was generally consistent across the majority of pre-specified subgroups, except for those with significant baseline anemia. Patients with baseline anemia appear to derive a substantial mortality benefit with transradial access rather than transoral access, compared to those with mild or no anemia. So, the authors concluded, that the meta-analysis provides evidence that transradial access should be considered the preferable access site for PCI, in patients with acute coronary syndrome, supporting most recent recommendations on the preferential use of this radial approach. So you were right, Greg. Dr. Greg Hundley: Very nice, Carolyn. A really important piece of science to disclose to our listeners, in that hurried state, and moving quickly door to balloon times, et cetera. And here we find another positive outcome in study result for transradial approaches. Well Carolyn, as we know, my next paper, it's really going to come to us from the world of preclinical science. And it pertains to hypertension, which is a common cardiovascular disease, and is related to both genetic and environmental factors. But the mechanisms linking the interplay between the domains of genetics and the environment have not been well studied. Now, DNA methylation, a classical epigenetic modification, not only regulates gene expression, but is also quite susceptible to environmental factors. Thereby, linking environmental factors to genetic modifications. So therefore, Carolyn, these authors, including Professor Jingzhou Chen, from Fuwai Hospital, National Center for Cardiovascular Diseases, and the Chinese Academy of Medical Sciences, and the Peking Union Medical College, and their colleagues, felt that screening differential genomic DNA methylation, in subjects with hypertension, would be important for investigating this genetic environment interplay in hypertension. So this study, Carolyn, like many from the world of preclinical science and circulation, incorporated both human and animal model subjects. Methodologically differential genomic DNA methylation in hypertensive, pre-hypertensive, and healthy control individuals, was screened using the Illumina 450K BeadChip, and then verified by pyrosequencing. Plasma oviduct glycoprotein 1, or OVGP1 levels, were determined using an enzyme-linked immunosorbent assay. And OVGP1 transgenic and knockout mice were generated to analyze the function of OVGP1. Dr. Carolyn Lam: Wow. Nice approach, Greg. And what did the authors find? Dr. Greg Hundley: Right, Carolyn. These authors found a hypomethylated site at cg20823859 in the promoter region of OVGP1, and the plasma OVGP1 levels were significantly increased in hypertensive patients. This finding indicates that OVGP1 is associated with hypertension. Now Carolyn, in OVGP1 transgenic mice, OVGP1 over expression caused an increase in blood pressure. Also, dysfunctional vasoconstriction, and vasodilation, remodeling of the arterial walls, and increased vascular superoxide stress and inflammation. And these phenomenon were exacerbated by angiotensin II infusion. In contrast, OVGP1 deficiency, attenuated angiotensin II induced vascular oxidase, stress, inflammation, and collagen deposition. Now pull down, and co-immunoprecipitation assays showed that myosin heavy chain 2A, or MYH9, interacted with OVGP1. Whereas, inhibition of MYH9 attenuated OVGP1 induced hypertension and vascular remodeling. Dr. Carolyn Lam: So Greg, let me try to summarize, is that okay? So hypomethylation, at that specific site in the promoter region of the OVGP1 gene, is associated with hypertension, and induces its upregulation. The interaction of this OVGP1 with myosin heavy chain 2A contributes to vascular remodeling and dysfunction. And so, OVGP1 is a pro hypertensive factor, that promotes vascular remodeling by binding to this myosin heavy chain. So, really cool stuff. Thanks for teaching us. Dr. Greg Hundley: Very good. Dr. Carolyn Lam: Well thanks so much, Greg. And we go back to the clinical world now, and ask the question, what is the efficacy and safety of prophylactic full dose anticoagulation and antiplatelet therapy, in critically ill COVID-19 patients? So I'm going to tell you the results of the COVID-PACT trial. And this was a multi-center, two-by-two factorial, open label, randomized controlled trial, with blinded endpoint adjudication in 390 ICU level patients. So, severely ill patients with COVID-19, from 34 US centers. Patients were randomized to a strategy of full dose anticoagulation, or standard dose prophylactic anticoagulation. And in the absence of an indication for antiplatelet therapy, patients were additionally randomized to either clopidogrel or no antiplatelet therapy. Dr. Greg Hundley: Ah, Carolyn. So what did they find? Dr. Carolyn Lam: Full dose anticoagulation substantially reduced the proportion of patients experiencing a venous or arterial thrombotic event, and there was no benefit from treatment with clopidogrel. Severe bleeding events were rare, but numerically increased in patients on full dose versus standard dose prophylactic anticoagulation, without any fatal bleeding events, GUSTO moderate or severe bleeding was so significantly increased with full dose anticoagulation, but with no difference in all-cause mortality. So in summary, in a population of critically ill patients with COVID-19, a strategy of prophylaxis with full dose, versus standard dose prophylactic anticoagulation, but not the addition of clopidogrel, reduced thrombotic complications, with an increased risk of bleeding, driven primarily by transfusions in hemodynamically stable patients, with no apparent excess in mortality. Dr. Greg Hundley: Very nice, Carolyn. What a important piece of information, as many of us around the world are taking care of critically ill patients with COVID-19. Well, how about we see what is in the mail bag this week? So first, Carolyn, there's a Frontiers piece by Dr. Packer, entitled, “Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 inhibitors, and Reaffirmation of the Nutrient Deprivation Signaling Autophagy Hypothesis.” Next, there's a Research Letter, from Professor Airaksinen entitled, “Novel Troponin Fragmentation Assay to Discriminate Between Troponin Elevations in Acute Myocardial Infarction and End-stage Renal Disease.” Carolyn, there's another Research Letter, from Professor Solomon, entitled, “Aptamer Proteomics for Biomarker Discovery in Heart Failure with Reduced Ejection Fraction.” Also, Carolyn, [a] wonderful Cardiovascular News summary from Tracy Hampton, reviewing three articles. First, “Mechanisms Behind Cannabis Effects on Heart Health.” The second, “Exercise Inducible Metabolite Suppresses Hunger.” And then lastly, “Piezo1 Initiates the Cardiomyocyte Hypertrophic Response to Pressure Overload.” Dr. Carolyn Lam: Cool. There's also an exchange of letters between Doctors Jha and Borlaug on latent pulmonary vascular disease in therapeutic atrial shunt. And finally, an On My Mind, by Dr. David Kass entitled, “What's EF Got To Do, Got To Do With It.” I love it. You must read it. It's so, so cool. All right. But now, let's go on to our feature discussion, shall we? Dr. Greg Hundley: You bet, Carolyn.   Welcome listeners, to our feature discussion today, and really delving into the world of in-hospital cardiac arrest, and how we manage those patients. And we have with us today, Dr. Kevin Roedl from Hamburg, Germany, Dr. Sebastian Wolfrum from Lubeck, Germany, and our own associate editor, Dr. Mark Link from University of Texas Southwestern in Dallas, Texas. Welcome gentlemen. Kevin, we're going to start with you. Can you describe for us, some of the background information that went into the construct of your study, and what was the hypothesis that you wanted to address? Dr. Kevin Roedl: Thank you, Greg. We thank you for the kind invitation to this podcast. We're very likened to do this podcast with you. And so, talking about the background of hypothermia in-hospital cardiac arrest, we have to go back like two decades almost, because there were two studies in New England Journal of Medicine published 2002, who introduced mild therapeutic hyperthermia to the treatment in post cardiac arrest. Primary, these two studies show the benefit of the therapy in this kind of patients. And then, 2003, it was introduced in also the international guidelines. However, these studies only addressed out-of-hospital cardiac arrest patients, and also, only shockable rhythms. And so, the question arised over the years, what about other patients like non shockable rhythms, or also in-hospital cardiac arrest? And so, that's basically was the primary aim of our study to address this special population. Because when you see the states, the numbers, there are 290,000 in-hospital cardiac arrests a year. So it's actually, a very large population. And there's no randomized control trial to show any benefit, or maybe harm, in this group. There were some observational studies, 2016 in China published. From China, in this group, they looked at the Get With The Guidelines registry, and actually, they saw that there was probably a negative influence of hypothermia in the study. However, it was only observational. So actually, there were no randomized control trials. And that primary hypothesis was, that we wanted to know actually, does thus mild therapeutic hyperthermia work in this group of patients in the in-hospital cardiac arrest setting? And what is the outcome? Is it like in the out-of-hospital cardiac arrest setting, or not? Dr. Greg Hundley: Wonderful, Kevin. And so, can you describe for us then, your study population and your study design? Dr. Kevin Roedl: Yes, of course. We did a randomized control trial. There were over 1000 people screened, and overall, we included 242. So you see how hard it is to get people in there. And actually, in terms of hypothermic temperature control, we are 120 about, and long term at 118, and the final others of the endpoints. And when we look at the baseline characters of these patients, they were well balanced actually, about 72 years. When we look at the initial cardiac arrest rhythm, that's interesting because about 70% non-shockable rhythms, and 25% shockable rhythms. And probably also interesting, the location of the cardiac arrest. Medical boards about 50%, and ICU or ED was 22%. So that's probably summed up the baseline characteristics of our study. Dr. Greg Hundley: Perfect. And so Kevin, can you describe for us what was the hypothermic target for the group that was going to have their temperature recused? Dr. Kevin Roedl: Yes, hypodermic target was 32 degrees to 44. And so two degrees Celsius, basically the same target like in earlier trials. Dr. Greg Hundley: Very nice. Well listeners, now we're going to turn to our second co-author, Dr. Sebastian Wolfrum. And Sebastian, can you share with us the study results? Dr. Sebastian Wolfrum: Yes, Greg. Thank you very much for the opportunity to participate in this podcast. Only wanted to include unconscious patients, and therefore, we took a time and took 45 minutes after their cardiac arrest, to let the patients get away if they did so. We also excluded patients that had severe functional deficit before the cardiac arrest; since we could not really define the neurological outcome if we would've included those. And we didn't see any differences. Neither in mortality, not in the functional outcome, either when they're treated with 33 degrees Celsius, or whether normothermia was used. The death rate after six month was in a range which is comparable to other in-hospital cardiac arrest studies, and higher than those performed in the out-of-hospital cardiac arrest studies. It was about slightly over 70% in both groups. And the number of patients with the good functional recovery after six months was 23% of the patients in the hypothermia group, and 24% of the patients in the normothermia group. And if we look at only the survivors, we see that the ones which are worse functional outcome, were most of them dead after six months. We then also focused on the temperature curves in our patients, and to see whether we have achieved our goal. And we saw that we have reached the target temperature within four and a half hours after cardiac arrest in our hypothermia group. Which is not as fast that we had expected, but still in the range, which is comparable to other studies on this field. And we also saw that our control group was about 37 degrees, within the first 12 and 48 hours. So we truly avoided fever, which has not been done in every previous study on cardiac arrests. Dr. Greg Hundley: Very nice. And any differences between the hypothermia and normothermia groups, related to the age of the patient? Or, whether or not they had a shockable rhythm at the time of presentation? Dr. Sebastian Wolfrum: We saw as a result of our study, that age is a predictive factor for mortality. But age did not differ between our treatment groups, and therefore, did not interfere with our results. And we didn't see differences in the shockable or non-shockable rate in our patients in the different treatment groups.   Dr. Greg Hundley: Thank you. Well listeners, now we're going to turn to our associate editor, Dr. Mark Link, one of our expert electrophysiologists at Circulation. And Mark, you have many papers come across your desk, and what attracted you to this particular paper? Dr. Mark Link: There were a number of things. One, it's hard to do RCTs in resuscitation, and I thought they did a very nice job with this RCT. Two, the subject of hypothermia, or therapeutic temperature management, is a very hot one in resuscitation. It's one of the few treatments in the past that have been shown to make a difference in outcome. And so, all of those trials were done in out-of-hospital arrest. So to have a trial done in in-hospital arrest was very intriguing also. And I think we're all disappointed that it wasn't a positive trial, but we have to take the negative trials also. And I think, part of the reason it may have been a negative trial is because the normal thermic group avoided hyperthermia. And I think that's something that's coming out of a lot of these trials is avoid fever. It may not be so important to get hypothermic targets, actually, looks like it's probably not, but it looks like it's very important to avoid fever. Dr. Greg Hundley: Very nice. Well listeners, we're going to turn back to our expert panel here really, and start with you Kevin. Kevin, what do you think is the next study that needs to be performed in this sphere of research? Dr. Kevin Roedl: Thank you for this interesting question. Yeah, a bunch of studies could be performed, especially maybe in the out-of-hospital cardiac arrest study, because we don't know. This fever harmful, we have to find certain subgroups in which this treatment works. So maybe in this subgroups there is data on this and it could be a benefit. So these are, I think, the two main topics that should be done in the future. Dr. Greg Hundley: Thank you. Sebastian, what are your thoughts? Dr. Sebastian Wolfrum: As Mark said, the hypothermic treatment was, for decades, maybe the only treatment which we could give to cardiac arrest patients, which has been proven to reduce mortality. And all other studies following didn't see any be benefit of hypothermia, not even in a subgroup. Also, the TTM trials did not. So I'm questioning myself, where is the original HACA study group that benefits? Where did this hide in the other studies? So I would think, to do another study in out-of-hospital cardiac arrest patients, whether in ventricular fibrillation that had shown in the HACA trial to reduce mortality. This should be done in a similar way to the original study, to see whether there is this subgroup. People who support the idea of hypothermia also focus very much on the fast onset of their hypothermic treatment. And they say we saw a difference in mortality in the HACA trial, and we could very fast. And I think the other studies have to show that they cool as fast as the HACA study. So the main focus should be on the time calls of hypothermia after cardiac arrest, cooling very fast to a target temperature of 33 degrees, maybe holding on for 24, maybe 48 hours. Dr. Greg Hundley: Very nice, Sebastian. So focusing on the speed and the timing of that cooling. And Mark, anything to add? Dr. Mark Link: Yeah, so if I sit here with my writing group hat on for the HA and say, "What are we going to do for the resuscitation guidelines in 2025?" I think you look at the totality of the data for targeted temperature management. And I think, the main thing you say, walking away from this, is avoid fever. Don't let your patients get hot. I'm not sure you can say much more than that right now, until we get more data. Dr. Greg Hundley: Very nice. Well listeners, a really interesting provocative discussion today. And we want to thank Dr. Kevin Roedl from Hamburg, Germany, Dr. Sebastian Wolfrum from Lubeck, Germany, and our own associate editor, Dr. Mark Link from Dallas, Texas, bringing us the results of this study highlighting that hypothermic temperature control is compared with normothermia did not improve survival, nor functional outcome, at 180 days in patients presenting with coma after in-hospital cardiac arrest. Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week On The Run. This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors, or of the American Heart Association. For more, please visit ahajournals.org.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Gene drives: why the wait?, published by Metacelsus on September 19, 2022 on LessWrong. (Crossposted from my Substack) If you've been following biology news over the last few years, you might have heard of an interesting concept called a “gene drive”. The overall idea is to engineer a genetic allele that transmits itself to all offspring of a sexually reproducing organism, instead of being inherited by 50% as usual. This allele can also perform some other biological function (a relevant example is causing female sterility). A gene drive spreads through a population. From Esvelt et al. 2014 (CC-BY) In multiple trials, modern CRISPR-based gene drives have shown high efficacy in spreading through populations of caged Anopheles mosquitoes and completely suppressing their reproduction. Since Anopheles mosquitoes are the only ones that transmit malaria, causing their extinction would directly save hundreds of thousands of lives per year. Similar gene drives targeted to other types of mosquitoes (Aedes, Culex, etc.) could also eliminate diseases such as dengue fever, Zika virus, and West Nile virus. However, in spite of promising laboratory trials, gene drives have not yet been deployed in the wild. But why not? History of gene drives Although the technology to build effective gene drives did not exist until recently, the idea has been around for a while. In fact, gene drives occur naturally. Some well-known examples are transposons in flies, homing endonucleases in algae, and segregation distorters in mice. The idea of engineering a site-specific nuclease as a gene drive was developed as early as 2003, and in the decade that followed there were several efforts to develop these, with the labs of Austin Burt and Andrea Crisanti taking a lead role. These early systems showed some biased inheritance, but were not stable for more than a few generations. The advent of CRISPR as a gene editing system opened up a new opportunity. A paper in 2014 by Kevin Esvelt and co-workers proposed Cas9 as a nuclease for a gene drive, with several properties making it ideal for the task. It lacks repetitive sequences that caused problems with earlier gene drives using zinc-finger nucleases or TALENs. It has a very high efficiency of cutting. It is easy to target a new site by simply changing the guide RNA. Several nearby sites could be targeted at once, using different guide RNAs. From Esvelt et al. 2014 (CC-BY) CRISPR-based gene drives quickly gained popularity in the field, and by 2018 the Crisanti lab had demonstrated a working gene drive that could efficiently suppress populations of Anopheles gambiae by targeting an exon of the doublesex gene required for female development. At the time this was announced, I was studying at the University of Cambridge, and attended a public lecture by Prof. Crisanti about his lab's work. The overall mood in the room was almost euphoric: here was a technology that could save millions of lives, the best thing since Borlaug's wheat! Since that lecture, about 2 million people, mostly children in Africa, have died of malaria. Gene drive research has not stood still: the Crisanti lab tested their doublesex drive in larger cages of mosquitoes, and it again completely eliminated the populations. But given the millions of lives at stake, what's taking so long for this gene drive to be released? See also: the battle against malaria in Africa has stalled Why the wait? There are two good arguments against the immediate release of gene drives to eliminate mosquitoes. First, nuclease gene drives have the possibility of generating resistant alleles, making future gene drives not work against the same target. Therefore, it's important to get it right the first time, otherwise the potential of gene drives could be wasted. The goal of the large cage trials I mentioned earli...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Gene drives: why the wait?, published by Metacelsus on September 19, 2022 on LessWrong. (Crossposted from my Substack) If you've been following biology news over the last few years, you might have heard of an interesting concept called a “gene drive”. The overall idea is to engineer a genetic allele that transmits itself to all offspring of a sexually reproducing organism, instead of being inherited by 50% as usual. This allele can also perform some other biological function (a relevant example is causing female sterility). A gene drive spreads through a population. From Esvelt et al. 2014 (CC-BY) In multiple trials, modern CRISPR-based gene drives have shown high efficacy in spreading through populations of caged Anopheles mosquitoes and completely suppressing their reproduction. Since Anopheles mosquitoes are the only ones that transmit malaria, causing their extinction would directly save hundreds of thousands of lives per year. Similar gene drives targeted to other types of mosquitoes (Aedes, Culex, etc.) could also eliminate diseases such as dengue fever, Zika virus, and West Nile virus. However, in spite of promising laboratory trials, gene drives have not yet been deployed in the wild. But why not? History of gene drives Although the technology to build effective gene drives did not exist until recently, the idea has been around for a while. In fact, gene drives occur naturally. Some well-known examples are transposons in flies, homing endonucleases in algae, and segregation distorters in mice. The idea of engineering a site-specific nuclease as a gene drive was developed as early as 2003, and in the decade that followed there were several efforts to develop these, with the labs of Austin Burt and Andrea Crisanti taking a lead role. These early systems showed some biased inheritance, but were not stable for more than a few generations. The advent of CRISPR as a gene editing system opened up a new opportunity. A paper in 2014 by Kevin Esvelt and co-workers proposed Cas9 as a nuclease for a gene drive, with several properties making it ideal for the task. It lacks repetitive sequences that caused problems with earlier gene drives using zinc-finger nucleases or TALENs. It has a very high efficiency of cutting. It is easy to target a new site by simply changing the guide RNA. Several nearby sites could be targeted at once, using different guide RNAs. From Esvelt et al. 2014 (CC-BY) CRISPR-based gene drives quickly gained popularity in the field, and by 2018 the Crisanti lab had demonstrated a working gene drive that could efficiently suppress populations of Anopheles gambiae by targeting an exon of the doublesex gene required for female development. At the time this was announced, I was studying at the University of Cambridge, and attended a public lecture by Prof. Crisanti about his lab's work. The overall mood in the room was almost euphoric: here was a technology that could save millions of lives, the best thing since Borlaug's wheat! Since that lecture, about 2 million people, mostly children in Africa, have died of malaria. Gene drive research has not stood still: the Crisanti lab tested their doublesex drive in larger cages of mosquitoes, and it again completely eliminated the populations. But given the millions of lives at stake, what's taking so long for this gene drive to be released? See also: the battle against malaria in Africa has stalled Why the wait? There are two good arguments against the immediate release of gene drives to eliminate mosquitoes. First, nuclease gene drives have the possibility of generating resistant alleles, making future gene drives not work against the same target. Therefore, it's important to get it right the first time, otherwise the potential of gene drives could be wasted. The goal of the large cage trials I mentioned earli...

Charles C. Mann is the author of three of my favorite history books: 1491. 1493, and The Wizard and the Prophet. We discuss:why Native American civilizations collapsed and why they failed to make more technological progresswhy he disagrees with Will MacAskill about longtermismwhy there aren't any successful slave revoltshow geoengineering can help us solve climate changewhy Bitcoin is like the Chinese Silver Tradeand much much more!Watch on YouTube. Listen on Apple Podcasts, Spotify, or any other podcast platform. Read the full transcript here. Some really cool guests coming up, subscribe to find out about future episodes!Follow me on Twitter for updates on future episodes.If you enjoyed this episode, you may also enjoy my interviews of Will MacAskill (about longtermism), Steve Hsu (about intelligence and embryo selection), and David Deutsch (about AI and the problems with America's constitution).If you end up enjoying this episode, I would be super grateful if you shared it. Post it on Twitter, send it to your friends & group-chats, and throw it up on any relevant subreddits & forums you follow. Can't exaggerate how much it helps a small podcast like mine.Timestamps(0:00:00) -Epidemically Alternate Realities(0:00:25) -Weak Points in Empires(0:03:28) -Slave Revolts(0:08:43) -Slavery Ban(0:12:46) - Contingency & The Pyramids(0:18:13) - Teotihuacan(0:20:02) - New Book Thesis(0:25:20) - Gender Ratios and Silicon Valley(0:31:15) - Technological Stupidity in the New World(0:41:24) - Religious Demoralization(0:44:00) - Critiques of Civilization Collapse Theories(0:49:05) - Virginia Company + Hubris(0:53:30) - China's Silver Trade(1:03:03) - Wizards vs. Prophets(1:07:55) - In Defense of Regulatory Delays(0:12:26) -Geoengineering(0:16:51) -Finding New Wizards(0:18:46) -Agroforestry is Underrated(1:18:46) -Longtermism & Free MarketsTranscriptDwarkesh Patel   Okay! Today I have the pleasure of speaking with Charles Mann, who is the author of three of my favorite books, including 1491: New Revelations of America before Columbus. 1493: Uncovering the New World Columbus Created, and The Wizard and the Prophet: Two Remarkable Scientists and Their Dueling Visions to Shape Tomorrow's World. Charles, welcome to the Lunar Society.Charles C. Mann   It's a pleasure to be here.Epidemically Alternate RealitiesDwarkesh Patel   My first question is: How much of the New World was basically baked into the cake? So at some point, people from Eurasia were going to travel to the New World, bringing their diseases. Considering disparities and where they would survive, if the Acemoglu theory that you cited is correct, then some of these places were bound to have good institutions and some of them were bound to have bad institutions. Plus, because of malaria, there were going to be shortages in labor that people would try to fix with African slaves. So how much of all this was just bound to happen? If Columbus hadn't done it, then maybe 50 years down the line, would someone from Italy have done it? What is the contingency here?Charles C. Mann   Well, I think that some of it was baked into the cake. It was pretty clear that at some point, people from Eurasia and the Western Hemisphere were going to come into contact with each other. I mean, how could that not happen, right? There was a huge epidemiological disparity between the two hemispheres––largely because by a quirk of evolutionary history, there were many more domesticable animals in Eurasia and the Eastern hemisphere. This leads almost inevitably to the creation of zoonotic diseases: diseases that start off in animals and jump the species barrier and become human diseases. Most of the great killers in human history are zoonotic diseases. When people from Eurasia and the Western Hemisphere meet, there are going to be those kinds of diseases. But if you wanted to, it's possible to imagine alternative histories. There's a wonderful book by Laurent Binet called Civilizations that, in fact, does just that. It's a great alternative history book. He imagines that some of the Vikings came and extended further into North America, bringing all these diseases, and by the time of Columbus and so forth, the epidemiological balance was different. So when Columbus and those guys came, these societies killed him, grabbed his boats, and went and conquered Europe. It's far-fetched, but it does say that this encounter would've happened and that the diseases would've happened, but it didn't have to happen in exactly the way that it did. It's also perfectly possible to imagine that Europeans didn't engage in wholesale slavery. There was a huge debate when this began about whether or not slavery was a good idea. There were a lot of reservations, particularly among the Catholic monarchy asking the Pope “Is it okay that we do this?” You could imagine the penny dropping in a slightly different way. So, I think some of it was bound to happen, but how exactly it happened was really up to chance, contingency, and human agency,Weak Points in EmpiresDwarkesh Patel   When the Spanish first arrived in the 15th and 16th centuries, were the Incas and the Aztecs at a particularly weak point or particularly decadent? Or was this just how well you should have expected this civilization to be functioning at any given time period?Charles C. Mann   Well, typically, empires are much more jumbly and fragile entities than we imagine. There's always fighting at the top. What Hernán Cortés was able to do, for instance, with the Aztecs––who are better called The Triple Alliance (the term “Aztec” is an invention from the 19th century). The Triple Alliance was comprised of three groups of people in central Mexico, the largest of which were the Mexica, who had the great city of Tenochtitlan. The other two guys really resented them and so what Cortes was able to do was foment a civil war within the Aztec empire: taking some enemies of the Aztec, some members of the Aztec empire, and creating an entirely new order. There's a fascinating set of history that hasn't really emerged into the popular consciousness. I didn't include it in 1491 or 1493 because it was so new that I didn't know anything about it; everything was largely from Spanish and Mexican scholars about the conquest within the conquest. The allies of the Spaniards actually sent armies out and conquered big swaths of northern and southern Mexico and Central America. So there's a far more complex picture than we realized even 15 or 20 years ago when I first published 1491. However, the conquest wasn't as complete as we think. I talk a bit about this in 1493 but what happens is Cortes moves in and he marries his lieutenants to these indigenous people, creating this hybrid nobility that then extended on to the Incas. The Incas were a very powerful but unstable empire and Pizarro had the luck to walk in right after a civil war. When he did that right after a civil war and massive epidemic, he got them at a very vulnerable point. Without that, it all would have been impossible. Pizarro cleverly allied with the losing side (or the apparently losing side in this in the Civil War), and was able to create a new rallying point and then attack the winning side. So yes, they came in at weak points, but empires typically have these weak points because of fratricidal stuff going on in the leadership.Dwarkesh Patel   It does also remind me of the East India Trading Company.Charles C. Mann   And the Mughal empire, yeah. Some of those guys in Bengal invited Clive and his people in. In fact, I was struck by this. I had just been reading this book, maybe you've heard of it: The Anarchy by William Dalrymple.Dwarkesh Patel   I've started reading it, yeah but I haven't made much progress.Charles C. Mann   It's an amazing book! It's so oddly similar to what happened. There was this fratricidal stuff going on in the Mughal empire, and one side thought, “Oh, we'll get these foreigners to come in, and we'll use them.” That turned out to be a big mistake.Dwarkesh Patel   Yes. What's also interestingly similar is the efficiency of the bureaucracy. Niall Ferguson has a good book on the British Empire and one thing he points out is that in India, the ratio between an actual English civil servant and the Indian population was about 1: 3,000,000 at the peak of the ratio. Which obviously is only possible if you have the cooperation of at least the elites, right? So it sounds similar to what you were saying about Cortes marrying his underlings to the nobility. Charles C. Mann   Something that isn't stressed enough in history is how often the elites recognize each other. They join up in arrangements that increase both of their power and exploit the poor schmucks down below. It's exactly what happened with the East India Company, and it's exactly what happened with Spain. It's not so much that there was this amazing efficiency, but rather, it was a mutually beneficial arrangement for Xcalack, which is now a Mexican state. It had its rights, and the people kept their integrity, but they weren't really a part of the Spanish Empire. They also weren't really wasn't part of Mexico until around 1857. It was a good deal for them. The same thing was true for the Bengalis, especially the elites who made out like bandits from the British Empire.Slave Revolts Dwarkesh Patel   Yeah, that's super interesting. Why was there only one successful slave revolt in the new world in Haiti? In many of these cases, the ratios between slaves and the owners are just huge. So why weren't more of them successful?Charles C. Mann   Well, you would first have to define ‘successful'. Haiti wasn't successful if you meant ‘creating a prosperous state that would last for a long time.' Haiti was and is (to no small extent because of the incredible blockade that was put on it by all the other nations) in terrible shape. Whereas in the case of Paul Maurice, you had people who were self-governing for more than 100 years.. Eventually, they were incorporated into the larger project of Brazil. There's a great Brazilian classic that's equivalent to what Moby Dick or Huck Finn is to us called Os Sertões by a guy named Cunha. And it's good! It's been translated into this amazing translation in English called ​​Rebellion in the Backlands. It's set in the 1880s, and it's about the creation of a hybrid state of runaway slaves, and so forth, and how they had essentially kept their independence and lack of supervision informally, from the time of colonialism. Now the new Brazilian state is trying to take control, and they fight them to the last person. So you have these effectively independent areas in de facto, if not de jure, that existed in the Americas for a very long time. There are some in the US, too, in the great dismal swamp, and you hear about those marooned communities in North Carolina, in Mexico, where everybody just agreed “these places aren't actually under our control, but we're not going to say anything.”  If they don't mess with us too much, we won't mess with them too much. Is that successful or not? I don't know.Dwarkesh Patel   Yeah, but it seems like these are temporary successes..Charles C. Mann   I mean, how long did nations last? Like Genghis Khan! How long did the Khan age last? But basically, they had overwhelming odds against them. There's an entire colonial system that was threatened by their existence. Similar to the reasons that rebellions in South Asia were suppressed with incredible brutality–– these were seen as so profoundly threatening to this entire colonial order that people exerted a lot more force against them than you would think would be worthwhile.Dwarkesh Patel   Right. It reminds me of James Scott's Against the Grain. He pointed out that if you look at the history of agriculture, there're many examples where people choose to run away as foragers in the forest, and then the state tries to bring them back into the fold.Charles C. Mann   Right. And so this is exactly part of that dynamic. I mean, who wants to be a slave, right? So as many people as possible ended up leaving. It's easier in some places than others.. it's very easy in Brazil. There are 20 million people in the Brazilian Amazon and the great bulk of them are the descendants of people who left slavery. They're still Brazilians and so forth, but, you know, they ended up not being slaves.Slavery BanDwarkesh Patel   Yeah, that's super fascinating. What is the explanation for why slavery went from being historically ever-present to ending at a particular time when it was at its peak in terms of value and usefulness? What's the explanation for why, when Britain banned the slave trade, within 100 or 200 years, there ended up being basically no legal sanction for slavery anywhere in the world?Charles C. Mann   This is a really good question and the real answer is that historians have been arguing about this forever. I mean, not forever, but you know, for decades, and there's a bunch of different explanations. I think the reason it's so hard to pin down is… kind of amazing. I mean, if you think about it, in 1800, if you were to have a black and white map of the world and put red in countries in which slavery was illegal and socially accepted, there would be no red anywhere on the planet. It's the most ancient human institution that there is. The Code of Hammurabi is still the oldest complete legal code that we have, and about a third of it is about rules for when you can buy slaves, when you can sell slaves, how you can mistreat them, and how you can't–– all that stuff. About a third of it is about buying, selling, and working other human beings. So this has been going on for a very, very long time. And then in a century and a half, it suddenly changes. So there's some explanation, and it's that machinery gets better. But the reason to have people is that you have these intelligent autonomous workers, who are like the world's best robots. From the point of view of the owner, they're fantastically good, except they're incredibly obstreperous and when they're caught, you're constantly afraid they're going to kill you. So if you have a chance to replace them with machinery, or to create a wage where you can run wage people, pay wage workers who are kept in bad conditions but somewhat have more legal rights, then maybe that's a better deal for you. Another one is that industrialization produced different kinds of commodities that became more and more valuable, and slavery was typically associated with the agricultural laborer. So as agriculture diminished as a part of the economy, slavery become less and less important and it became easier to get rid of them. Another one has to do with the beginning of the collapse of the colonial order. Part of it has to do with.. (at least in the West, I don't know enough about the East) the rise of a serious abolition movement with people like Wilberforce and various Darwins and so forth. And they're incredibly influential, so to some extent, I think people started saying, “Wow, this is really bad.”  I suspect that if you looked at South Asia and Africa, you might see similar things having to do with a social moment, but I just don't know enough about that. I know there's an anti-slavery movement and anti-caste movement in which we're all tangled up in South Asia, but I just don't know enough about it to say anything intelligent.Dwarkesh Patel   Yeah, the social aspect of it is really interesting. The things you mentioned about automation, industrialization, and ending slavery… Obviously, with time, that might have actually been why it expanded, but its original inception in Britain happened before the Industrial Revolution took off. So that was purely them just taking a huge loss because this movement took hold. Charles C. Mann   And the same thing is true for Bartolome de Las Casas. I mean, Las Casas, you know, in the 1540s just comes out of nowhere and starts saying, “Hey! This is bad.” He is the predecessor of the modern human rights movement. He's an absolutely extraordinary figure, and he has huge amounts of influence. He causes Spain's king in the 1540s to pass what they call The New Laws which says no more slavery, which is a devastating blow enacted to the colonial economy in Spain because they depended on having slaves to work in the silver mines in the northern half of Mexico and in Bolivia, which was the most important part of not only the Spanish colonial economy but the entire Spanish empire. It was all slave labor. And they actually tried to ban it. Now, you can say they came to their senses and found a workaround in which it wasn't banned. But it's still… this actually happened in the 1540s. Largely because people like Las Casas said, “This is bad! you're going to hell doing this.”Contingency & The Pyramids Dwarkesh Patel   Right. I'm super interested in getting into The Wizard and the Prophet section with you. Discussing how movements like environmentalism, for example, have been hugely effective. Again, even though it probably goes against the naked self-interest of many countries. So I'm very interested in discussing that point about why these movements have been so influential!But let me continue asking you about globalization in the world. I'm really interested in how you think about contingency in history, especially given that you have these two groups of people that have been independently evolving and separated for tens of thousands of years. What things turn out to be contingent? What I find really interesting from the book was how both of them developed pyramids––  who would have thought that structure would be within our extended phenotype or something?Charles C. Mann    It's also geometry! I mean, there's only a certain limited number of ways you can pile up stone blocks in a stable way. And pyramids are certainly one of them. It's harder to have a very long-lasting monument that's a cylinder. Pyramids are also easier to build: if you get a cylinder, you have to have scaffolding around it and it gets harder and harder.With pyramids, you can use each lower step to put the next one, on and on, and so forth. So pyramids seem kind of natural to me. Now the material you make them up of is going to be partly determined by what there is. In Cahokia and in the Mississippi Valley, there isn't a lot of stone. So people are going to make these earthen pyramids and if you want them to stay on for a long time, there's going to be certain things you have to do for the structure which people figured out. For some pyramids, you had all this marble around them so you could make these giant slabs of marble, which seems, from today's perspective, incredibly wasteful. So you're going to have some things that are universal like that, along with the apparently universal, or near-universal idea that people who are really powerful like to identify themselves as supernatural and therefore want to be commemorated. Dwarkesh Patel   Yes, I visited Mexico City recently.Charles C. Mann Beautiful city!TeotihuacanDwarkesh Patel Yeah, the pyramids there… I think I was reading your book at the time or already had read your book. What struck me was that if I remember correctly, they didn't have the wheel and they didn't have domesticated animals. So if you really think about it, that's a really huge amount of human misery and toil it must have taken to put this thing together as basically a vanity project. It's like a huge negative connotation if you think about what it took to construct it.Charles C. Mann   Sure, but there are lots of really interesting things about Teotihuacan. This is just one of those things where you can only say so much in one book. If I was writing the two-thousand-page version of 1491, I would have included this. So Tehuácan pretty much starts out as a standard Imperial project, and they build all these huge castles and temples and so forth. There's no reason to suppose it was anything other than an awful experience (like building the pyramids), but then something happened to Teotihuacan that we don't understand. All these new buildings started springing up during the next couple of 100 years, and they're all very very similar. They're like apartment blocks and there doesn't seem to be a great separation between rich and poor. It's really quite striking how egalitarian the architecture is because that's usually thought to be a reflection of social status. So based on the way it looks, could there have been a political revolution of some sort? Where they created something much more egalitarian, probably with a bunch of good guy kings who weren't interested in elevating themselves so much? There's a whole chapter in the book by David Wingrove and David Graeber, The Dawn of Everything about this, and they make this argument that Tehuácan is an example that we can look at as an ancient society that was much more socially egalitarian than we think. Now, in my view, they go a little overboard–– it was also an aggressive imperial power and it was conquering much of the Maya world at the same time. But it is absolutely true that something that started out one way can start looking very differently quite quickly. You see this lots of times in the Americas in the Southwest–– I don't know if you've ever been to Chaco Canyon or any of those places, but you should absolutely go! Unfortunately, it's hard to get there because of the roads terrible but overall, it's totally worth it. It's an amazing place. Mesa Verde right north of it is incredible, it's just really a fantastic thing to see. There are these enormous structures in Chaco Canyon, that we would call castles if they were anywhere else because they're huge. The biggest one, Pueblo Bonito, is like 800 rooms or some insane number like that. And it's clearly an imperial venture, we know that because it's in this canyon and one side is getting all the good light and good sun–– a whole line of these huge castles. And then on the other side is where the peons lived. We also know that starting around 1100, everybody just left! And then their descendants start the Puebla, who are these sort of intensely socially egalitarian type of people. It looks like a political revolution took place. In fact, in the book I'm now writing, I'm arguing (in a sort of tongue-in-cheek manner but also seriously) that this is the first American Revolution! They got rid of these “kings” and created these very different and much more egalitarian societies in which ordinary people had a much larger voice about what went on.Dwarkesh Patel   Interesting. I think I got a chance to see the Teotihuacan apartments when I was there, but I wonder if we're just looking at the buildings that survived. Maybe the buildings that survived were better constructed because they were for the elites? The way everybody else lived might have just washed away over the years.Charles C. Mann   So what's happened in the last 20 years is basically much more sophisticated surveys of what is there. I mean, what you're saying is absolutely the right question to ask. Are the rich guys the only people with things that survived while the ordinary people didn't? You can never be absolutely sure, but what they did is they had these ground penetrating radar surveys, and it looks like this egalitarian construction extends for a huge distance. So it's possible that there are more really, really poor people. But at least you'd see an aggressively large “middle class” getting there, which is very, very different from the picture you have of the ancient world where there's the sun priest and then all the peasants around them.New Book ThesisDwarkesh Patel   Yeah. By the way, is the thesis of the new book something you're willing to disclose at this point? It's okay if you're not––Charles C. Mann   Sure sure, it's okay! This is a sort of weird thing, it's like a sequel or offshoot of 1491. That book, I'm embarrassed to say, was supposed to end with another chapter. The chapter was going to be about the American West, which is where I grew up, and I'm very fond of it. And apparently, I had a lot to say because when I outlined the chapter; the outline was way longer than the actual completed chapters of the rest of the book. So I sort of tried to chop it up and so forth, and it just was awful. So I just cut it. If you carefully look at 1491, it doesn't really have an ending. At the end, the author sort of goes, “Hey! I'm ending, look at how great this is!” So this has been bothering me for 15 years. During the pandemic, when I was stuck at home like so many other people, I held out what I had since I've been saving string and tossing articles that I came across into a folder, and I thought, “Okay, I'm gonna write this out more seriously now.” 15 or 20 years later. And then it was pretty long so I thought “Maybe this could be an e-book.” then I showed it to my editor. And he said, “That is not an e-book. That's an actual book.” So I take a chapter and hope I haven't just padded it, and it's about the North American West. My kids like the West, and at various times, they've questioned what it would be like to move out there because I'm in Massachusetts, where they grew up. So I started thinking “What is the West going to be like, tomorrow? When I'm not around 30 or 50 years from now?”It seems to be that you won't know who's president or who's governor or anything, but there are some things we can know. It'd be hotter and drier than it is now or has been in the recent past, like that wouldn't really be a surprise. So I think we can say that it's very likely to be like that. All the projections are that something like 40% of the people in the area between the Mississippi and the Pacific will be of Latino descent–– from the south, so to speak. And there's a whole lot of people from Asia along the Pacific coast, so it's going to be a real ethnic mixing ground. There's going to be an epicenter of energy, sort of no matter what happens. Whether it's solar, whether it's wind, whether it's petroleum, or hydroelectric, the West is going to be economically extremely powerful, because energy is a fundamental industry.And the last thing is (and this is the iffiest of the whole thing), but I'm going to go out on a limb and say that the ongoing recuperation of sovereignty by the 294 federally recognized Native nations in the West is going to continue. That's been going in this very jagged way, but definitely for the last 50 or 60 years, as long as I've been around, the overall trend is in a very clear direction. So then you think, okay, this West is going to be wildly ethnically diverse, full of competing sovereignties and overlapping sovereignties. Nature is also going to really be in kind of a terminal. Well, that actually sounds like the 1200s! And the conventional history starts with Lewis and Clark and so forth. There's this breakpoint in history when people who looked like me came in and sort of rolled in from the East and kind of took over everything. And the West disappears! That separate entity, the native people disappear, and nature is tamed. That's pretty much what was in the textbooks when I was a kid. Do you know who Frederick Jackson Turner is? Dwarkesh Patel  No.Charles C. Mann So he's like one of these guys where nobody knows who he is. But he was incredibly influential in setting intellectual ideas. He wrote this article in 1893, called The Significance of the Frontier. It was what established this idea that there's this frontier moving from East to West and on this side was savagery and barbarism, and on this other side of civilization was team nature and wilderness and all that. Then it goes to the Pacific, and that's the end of the West. That's still in the textbooks but in a different form: we don't call native people “lurking savages” as he did. But it's in my kids' textbooks. If you have kids, it'll very likely be in their textbook because it's such a bedrock. What I'm saying is that's actually not a useful way to look at it, given what's coming up. A wonderful Texas writer, Bruce Sterling, says, “To know the past, you first have to understand the future.”It's funny, right? But what he means is that all of us have an idea of where the trajectory of history is going. A whole lot of history is about asking, “How did we get here? How do we get there?” To get that, you have to have an idea of what the “there” is. So I'm saying, I'm writing a history of the West with that West that I talked about in mind. Which gives you a very different picture: a lot more about indigenous fire management, the way the Hohokam survived the drought of the 1200s, and a little bit less about Billy the Kid. Gender Ratios and Silicon Valley Dwarkesh Patel   I love that quote hahaha. Speaking of the frontier, maybe it's a mistaken concept, but I remember that in a chapter of 1493, you talk about these rowdy adventurer men who outnumber the women in the silver mines and the kind of trouble that they cause. I wonder if there's some sort of distant analogy to the technology world or Silicon Valley, where you have the same kind of gender ratio and you have the same kind of frontier spirit? Maybe not the same physical violence––– more sociologically. Is there any similarity there?Charles C. Mann   I think it's funny, I hadn't thought about it. But it's certainly funny to think about. So let me do this off the top of my head. I like the idea that at the end of it, I can say, “wait, wait, that's ridiculous.“ Both of them would attract people who either didn't have much to lose, or were oblivious about what they had to lose, and had a resilience towards failure. I mean, it's amazing, the number of people in Silicon Valley who have completely failed at numbers of things! They just get up and keep‌ trying and have a kind of real obliviousness to social norms. It's pretty clear they are very much interested in making a mark and making their fortunes themselves. So there's at least a sort of shallow comparison, there are some certain similarities. I don't think this is entirely flattering to either group. It's absolutely true that those silver miners in Bolivia, and in northern‌ Mexico, created to a large extent, the modern world. But it's also true that they created these cesspools of violence and exploitation that had consequences we're still living with today. So you have to kind of take the bitter with the sweet. And I think that's true of Silicon Valley and its products *chuckles* I use them every day, and I curse them every day.Dwarkesh Patel   Right.Charles C. Mann   I want to give you an example. The internet has made it possible for me to do something like write a Twitter thread, get millions of people to read it, and have a discussion that's really amazing at the same time. Yet today, The Washington Post has an article about how every book in Texas (it's one of the states) a child checks out of the school library goes into a central state databank. They can see and look for patterns of people taking out “bad books” and this sort of stuff. And I think “whoa, that's really bad! That's not so good.” It's really the same technology that brings this dissemination and collection of vast amounts of information with relative ease. So with all these things, you take the bitter with the sweet. Technological Stupidity in the New WorldDwarkesh Patel   I want to ask you again about contingency because there are so many other examples where things you thought would be universal actually don't turn out to be. I think you talked about how the natives had different forms of metallurgy, with gold and copper, but then they didn't do iron or steel. You would think that given their “warring nature”, iron would be such a huge help. There's a clear incentive to build it. Millions of people living there could have built or developed this technology. Same with the steel, same with the wheel. What's the explanation for why these things you think anybody would have come up with didn't happen?Charles C. Mann   I know. It's just amazing to me! I don't know. This is one of those things I think about all the time. A few weeks ago, it rained, and I went out to walk the dog. I'm always amazed that there are literal glistening drops of water on the crabgrass and when you pick it up, sometimes there are little holes eaten by insects in the crabgrass. Every now and then, if you look carefully, you'll see a drop of water in one of those holes and it forms a lens. And you can look through it! You can see that it's not a very powerful lens by any means, but you can see that things are magnified. So you think “How long has there been crabgrass? Or leaves? And water?”  Just forever! We've had glass forever! So how is it that we had to wait for whoever it was to create lenses? I just don't get it. In book 1491, I mentioned the moldboard plow, which is the one with a curving blade that allows you to go through the soil much more easily. It was invented in China thousands of years ago, but not around in Europe until the 1400s. Like, come on, guys! What was it? And so, you know, there's this mysterious sort of mass stupidity. One of the wonderful things about globalization and trade and contact is that maybe not everybody is as blind as you and you can learn from them. I mean, that's the most wonderful thing about trade. So in the case of the wheel, the more amazing thing is that in Mesoamerica, they had the wheel on child's toys. Why didn't they develop it? The best explanation I can get is they didn't have domestic animals. A cart then would have to be pulled by people. That would imply that to make the cart work, you'd have to cut a really good road. Whereas they had these travois, which are these things that you hold and they have these skids that are shaped kind of like an upside-down V. You can drag them across rough ground, you don't need a road for them. That's what people used in the Great Plains and so forth. So you look at this, and you think “maybe this was the ultimate way to save labor. I mean, this was good enough. And you didn't have to build and maintain these roads to make this work”  so maybe it was rational or just maybe they're just blinkered. I don't know. As for assembly with steel, I think there's some values involved in that. I don't know if you've ever seen one of those things they had in Mesoamerica called Macuahuitl. They're wooden clubs with obsidian blades on them and they are sharp as hell. You don't run your finger along the edge because they just slice it open. An obsidian blade is pretty much sharper than any iron or steel blade and it doesn't rust. Nice. But it's much more brittle. So okay, they're there, and the Spaniards were really afraid of them. Because a single blow from these heavy sharp blades could kill a horse. They saw people whack off the head of a horse carrying a big strong guy with a single blow! So they're really dangerous, but they're not long-lasting. Part of the deal was that the values around conflict were different in the sense that conflict in Mesoamerica wasn't a matter of sending out foot soldiers in grunts, it was a chance for soldiers to get individual glory and prestige. This was associated with having these very elaborately beautiful weapons that you killed people with. So maybe not having steel worked better for their values and what they were trying to do at war. That would've lasted for years and I mean, that's just a guess. But you can imagine a scenario where they're not just blinkered but instead expressive on the basis of their different values. This is hugely speculative. There's a wonderful book by Ross Hassig about old Aztec warfare. It's an amazing book which is about the military history of The Aztecs and it's really quite interesting. He talks about this a little bit but he finally just says we don't know why they didn't develop all these technologies, but this worked for them.Dwarkesh Patel   Interesting. Yeah, it's kind of similar to China not developing gunpowder into an actual ballistic material––Charles C. Mann   Or Japan giving up the gun! They actually banned guns during the Edo period. The Portuguese introduced guns and the Japanese used them, and they said “Ahhh nope! Don't want them.” and they banned them. This turned out to be a terrible idea when Perry came in the 1860s. But for a long time, supposedly under the Edo period, Japan had the longest period of any nation ever without a foreign war. Dwarkesh Patel   Hmm. Interesting. Yeah, it's concerning when you think the lack of war might make you vulnerable in certain ways. Charles C. Mann   Yeah, that's a depressing thought.Religious DemoralizationDwarkesh Patel   Right. In Fukuyama's The End of History, he's obviously arguing that liberal democracy will be the final form of government everywhere. But there's this point he makes at the end where he's like, “Yeah, but maybe we need a small war every 50 years or so just to make sure people remember how bad it can get and how to deal with it.” Anyway, when the epidemic started in the New World, surely the Indians must have had some story or superstitious explanation–– some way of explaining what was happening. What was it?Charles C. Mann   You have to remember, the germ theory of disease didn't exist at the time. So neither the Spaniards, or the English, or the native people, had a clear idea of what was going on. In fact, both of them thought of it as essentially a spiritual event, a religious event. You went into areas that were bad, and the air was bad. That was malaria, right? That was an example. To them, it was God that was in control of the whole business. There's a line from my distant ancestor––the Governor Bradford of Plymouth Colony, who's my umpteenth, umpteenth grandfather, that's how waspy I am, he's actually my ancestor––about how God saw fit to clear the natives for us. So they see all of this in really religious terms, and more or less native people did too! So they thought over and over again that “we must have done something bad for this to have happened.” And that's a very powerful demoralizing thing. Your God either punished you or failed you. And this was it. This is one of the reasons that Christianity was able to make inroads. People thought “Their god is coming in and they seem to be less harmed by these diseases than people with our God.” Now, both of them are completely misinterpreting what's going on! But if you have that kind of spiritual explanation, it makes sense for you to say, “Well, maybe I should hit up their God.”Critiques of Civilization Collapse TheoriesDwarkesh Patel   Yeah, super fascinating. There's been a lot of books written in the last few decades about why civilizations collapse. There's Joseph Tainter's book, there's Jared Diamond's book. Do you feel like any of them actually do a good job of explaining how these different Indian societies collapsed over time?Charles C. Mann   No. Well not the ones that I've read. And there are two reasons for that. One is that it's not really a mystery. If you have a society that's epidemiologically naive, and smallpox sweeps in and kills 30% of you, measles kills 10% of you, and this all happens in a short period of time, that's really tough! I mean COVID killed one million people in the United States. That's 1/330th of the population. And it wasn't even particularly the most economically vital part of the population. It wasn't kids, it was elderly people like my aunt–– I hope I'm not sounding callous when I'm describing it like a demographer. Because I don't mean it that way. But it caused enormous economic damage and social conflict and so forth. Now, imagine something that's 30 or 40 times worse than that, and you have no explanation for it at all. It's kind of not a surprise to me that this is a super challenge. What's actually amazing is the number of nations that survived and came up with ways to deal with this incredible loss.That relates to the second issue, which is that it's sort of weird to talk about collapse in the ways that they sometimes do. Like both of them talk about the Mayan collapse. But there are 30 million Mayan people still there. They were never really conquered by the Spaniards. The Spaniards were still waging giant wars in Yucatan in the 1590s. In the early 21st century, I went with my son to Chiapas, which is the southernmost exit province. And that is where the Commandante Cero and the rebellions were going on. We were looking at some Mayan ruins, and they were too beautiful, and I stayed too long, and we were driving back through the night on these terrible roads. And we got stopped by some of these guys with guns. I was like, “Oh God, not only have I got myself into this, I got my son into this.” And the guy comes and looks at us and says, “Who are you?” And I say that we're American tourists. And he just gets this disgusted look, and he says, “Go on.” And you know, the journalist in me takes over and I ask, “What do you mean, just go on?” And he says, “We're hunting for Mexicans.” And as I'm driving I'm like “Wait a minute, I'm in Mexico.” And that those were Mayans. All those guys were Maya people still fighting against the Spaniards. So it's kind of funny to say that their society collapsed when there are Mayan radio stations, there are Maya schools, and they're speaking Mayan in their home. It's true, they don't have giant castles anymore. But, it's odd to think of that as collapse. They seem like highly successful people who have dealt pretty well with a lot of foreign incursions. So there's this whole aspect of “What do you mean collapse?” And you see that in Against the Grain, the James Scott book, where you think, “What do you mean barbarians?” If you're an average Maya person, working as a farmer under the purview of these elites in the big cities probably wasn't all that great. So after the collapse, you're probably better off. So all of that I feel is important in this discussion of collapse. I think it's hard to point to collapses that either have very clear exterior causes or are really collapses of the environment. Particularly the environmental sort that are pictured in books like Diamond has, where he talks about Easter Island. The striking thing about that is we know pretty much what happened to all those trees. Easter Island is this little speck of land, in the middle of the ocean, and Dutch guys come there and it's the only wood around for forever, so they cut down all the trees to use it for boat repair, ship repair, and they enslave most of the people who are living there. And we know pretty much what happened. There's no mystery about it.Virginia Company + HubrisDwarkesh Patel   Why did the British government and the king keep subsidizing and giving sanctions to the Virginia Company, even after it was clear that this is not especially profitable and half the people that go die? Why didn't they just stop?Charles C. Mann   That's a really good question. It's a super good question. I don't really know if we have a satisfactory answer, because it was so stupid for them to keep doing that. It was such a loss for so long. So you have to say, they were thinking, not purely economically. Part of it is that the backers of the Virginia Company, in sort of classic VC style, when things were going bad, they lied about it. They're burning through their cash, they did these rosy presentations, and they said, “It's gonna be great! We just need this extra money.” Kind of the way that Uber did. There's this tremendous burn rate and now the company says you're in tremendous trouble because it turns out that it's really expensive to provide all these calves and do all this stuff. The cheaper prices that made people like me really happy about it are vanishing. So, you know, I think future business studies will look at those rosy presentations and see that they have a kind of analogy to the ones that were done with the Virginia Company. A second thing is that there was this dog-headed belief kind of based on the inability to understand longitude and so forth, that the Americas were far narrower than they actually are. I reproduced this in 1493. There were all kinds of maps in Britain at the time showing these little skinny Philippines-like islands. So there's the thought that you just go up the Chesapeake, go a couple 100 miles, and you're gonna get to the Pacific into China. So there's this constant searching for a passage to China through this thought to be very narrow path. Sir Francis Drake and some other people had shown that there was a West Coast so they thought the whole thing was this narrow, Panama-like landform. So there's this geographical confusion. Finally, there's the fact that the Spaniards had found all this gold and silver, which is an ideal commodity, because it's not perishable: it's small, you can put it on your ship and bring it back, and it's just great in every way. It's money, essentially. Basically, you dig up money in the hills and there's this long-standing belief that there's got to be more of that in the Americas, we just need to find out where. So there's always that hope. Lastly, there's the Imperial bragging rights. You know, we can't be the only guys with a colony. You see that later in the 19th century when Germany became a nation and one of the first things the Dutch said was “Let's look for pieces of Africa that the rest of Europe hasn't claimed,” and they set up their own mini colonial empire. So there's this kind of “Keeping Up with the Joneses” aspect, it just seems to be sort of deep in the European ruling class. So then you got to have an empire that in this weird way, seems very culturally part of it. I guess it's the same for many other places. As soon as you feel like you have a state together, you want to index other things. You see that over and over again, all over the world. So that's part of it. All those things, I think, contributed to this. Outright lying, this delusion, other various delusions, plus hubris.Dwarkesh Patel   It seems that colonial envy has today probably spread to China. I don't know too much about it, but I hear that the Silk Road stuff they're doing is not especially economically wise. Is this kind of like when you have the impulse where if you're a nation trying to rise, you have that “I gotta go here, I gotta go over there––Charles C. Mann   Yeah and “Show what a big guy I am. Yeah,––China's Silver TradeDwarkesh Patel   Exactly. So speaking of China, I want to ask you about the silver trade. Excuse another tortured analogy, but when I was reading that chapter where you're describing how the Spanish silver was ending up with China and how the Ming Dynasty caused too much inflation. They needed more reliable mediums of exchange, so they had to give up real goods from China, just in order to get silver, which is just a medium of exchange––but it's not creating more apples, right? I was thinking about how this sounds a bit like Bitcoin today, (obviously to a much smaller magnitude) but in the sense that you're using up goods. It's a small amount of electricity, all things considered, but you're having to use up real energy in order to construct this medium of exchange. Maybe somebody can claim that this is necessary because of inflation or some other policy mistake and you can compare it to the Ming Dynasty. But what do you think about this analogy? Is there a similar situation where real goods are being exchanged for just a medium of exchange?Charles C. Mann   That's really interesting. I mean, on some level, that's the way money works, right? I go into a store, like a Starbucks and I buy a coffee, then I hand them a piece of paper with some drawings on it, and they hand me an actual coffee in return for a piece of paper. So the mysteriousness of money is kind of amazing. History is of course replete with examples of things that people took very seriously as money. Things that to us seem very silly like the cowry shell or in the island of Yap where they had giant stones! Those were money and nobody ever carried them around. You transferred the ownership of the stone from one person to another person to buy something. I would get some coconuts or gourds or whatever, and now you own that stone on the hill. So there's a tremendous sort of mysteriousness about the human willingness to assign value to arbitrary things such as (in Bitcoin's case) strings of zeros and ones. That part of it makes sense to me. What's extraordinary is when the effort to create a medium of exchange ends up costing you significantly–– which is what you're talking about in China where people had a medium of exchange, but they had to work hugely to get that money. I don't have to work hugely to get a $1 bill, right? It's not like I'm cutting down a tree and smashing the papers to pulp and printing. But you're right, that's what they're kind of doing in China. And that's, to a lesser extent, what you're doing in Bitcoin. So I hadn't thought about this, but Bitcoin in this case is using computer cycles and energy. To me, it's absolutely extraordinary the degree to which people who are Bitcoin miners are willing to upend their lives to get cheap energy. A guy I know is talking about setting up small nuclear plants as part of his idea for climate change and he wants to set them up in really weird remote areas. And I was asking “Well who would be your customers?” and he says Bitcoin people would move to these nowhere places so they could have these pocket nukes to privately supply their Bitcoin habits. And that's really crazy! To completely upend your life to create something that you hope is a medium of exchange that will allow you to buy the things that you're giving up. So there's a kind of funny aspect to this. That was partly what was happening in China. Unfortunately, China's very large, so they were able to send off all this stuff to Mexico so that they could get the silver to pay their taxes, but it definitely weakened the country.Wizards vs. ProphetsDwarkesh Patel   Yeah, and that story you were talking about, El Salvador actually tried it. They were trying to set up a Bitcoin city next to this volcano and use the geothermal energy from the volcano to incentivize people to come there and mine cheap Bitcoin. Staying on the theme of China, do you think the prophets were more correct, or the wizards were more correct for that given time period? Because we have the introduction of potato, corn, maize, sweet potatoes, and this drastically increases the population until it reaches a carrying capacity. Obviously, what follows is the other kinds of ecological problems this causes and you describe these in the book. Is this evidence of the wizard worldview that potatoes appear and populations balloon? Or are the prophets like “No, no, carrying capacity will catch up to us eventually.”Charles C. Mann   Okay, so let me interject here. For those members of your audience who don't know what we're talking about. I wrote this book, The Wizard and the Prophet. And it's about these two camps that have been around for a long time who have differing views regarding how we think about energy resources, the environment, and all those issues. The wizards, that's my name for them––Stuart Brand called them druids and, in fact, originally, the title was going to involve the word druid but my editor said, “Nobody knows what a Druid is” so I changed it into wizards–– and anyway the wizards would say that science and technology properly applied can allow you to produce your way out of these environmental dilemmas. You turn on the science machine, essentially, and then we can escape these kinds of dilemmas. The prophets say “No. Natural systems are governed by laws and there's an inherent carrying capacity or limit or planetary boundary.” there are a bunch of different names for them that say you can't do more than so much.So what happened in China is that European crops came over. One of China's basic geographical conditions is that it's 20% of the Earth's habitable surface area, or it has 20% of the world's population, but only has seven or 8% of the world's above-ground freshwater. There are no big giant lakes like we have in the Great Lakes. And there are only a couple of big rivers, the Yangtze and the Yellow River. The main staple crop in China has to be grown in swimming pools, and that's you know, rice. So there's this paradox, which is “How do you keep people fed with rice in a country that has very little water?” If you want a shorthand history of China, that's it. So prophets believe that there are these planetary boundaries. In history, these are typically called Malthusian Limits after Malthus and the question is: With the available technology at a certain time, how many people can you feed before there's misery?The great thing about history is it provides evidence for both sides. Because in the short run, what happened when American crops came in is that the potato, sweet potato, and maize corn were the first staple crops that were dryland crops that could be grown in the western half of China, which is very, very dry and hot and mountainous with very little water. Population soars immediately afterward, but so does social unrest, misery, and so forth. In the long run, that becomes adaptable when China becomes a wealthy and powerful nation. In the short run, which is not so short (it's a couple of centuries), it really causes tremendous chaos and suffering. So, this provides evidence for both sides. One increases human capacity, and the second unquestionably increases human numbers and that leads to tremendous erosion, land degradation, and human suffering.Dwarkesh Patel   Yeah, that's a thick coin with two sides. By the way, I realized I haven't gotten to all the Wizard and Prophet questions, and there are a lot of them. So I––Charles C. Mann   I certainly have time! I'm enjoying the conversation. One of the weird things about podcasts is that, as far as I can tell, the average podcast interviewer is far more knowledgeable and thoughtful than the average sort of mainstream journalist interviewer and I just find that amazing. I don't understand it. So I think you guys should be hired. You know, they should make you switch roles or something.Dwarkesh Patel   Yeah, maybe. Charles C. Mann   It's a pleasure to be asked these interesting questions about subjects I find fascinating.Dwarkesh Patel   Oh, it's my pleasure to get to talk to you and to get to ask these questions. So let me ask about the Wizard and the Prophet. I just interviewed WIll McCaskill, and we were talking about what ends up mattering most in history. I asked him about Norman Borlaug and said that he's saved a billion lives. But then McCaskill pointed out, “Well, that's an exceptional result” and he doesn't think the technology is that contingent. So if Borlaug hadn't existed, somebody else would have discovered what he discovered about short wheat stalks anyways. So counterfactually, in a world where Ebola doesn't exist, it's not like a billion people die, maybe a couple million more die until the next guy comes around. That was his view. Do you agree? What is your response?Charles C. Mann   To some extent, I agree. It's very likely that in the absence of one scientist, some other scientist would have discovered this, and I mentioned in the book, in fact, that there's a guy named Swaminathan, a remarkable Indian scientist, who's a step behind him and did much of the same work. At the same time, the individual qualities of Borlaug are really quite remarkable. The insane amount of work and dedication that he did.. it's really hard to imagine. The fact is that he was going against many of the breeding plant breeding dogmas of his day, that all matters! His insistence on feeding the poor… he did remarkable things. Yes, I think some of those same things would have been discovered but it would have been a huge deal if it had taken 20 years later. I mean, that would have been a lot of people who would have been hurt in the interim! Because at the same time, things like the end of colonialism, the discovery of antibiotics, and so forth, were leading to a real population rise, and the amount of human misery that would have occurred, it's really frightening to think about. So, in some sense, I think he's (Will McCaskill) right. But I wouldn't be so glib about those couple of million people.Dwarkesh Patel   Yeah. And another thing you might be concerned about is that given the hostile attitude that people had towards the green revolution right after, if the actual implementation of these different strains of biochar sent in India, if that hadn't been delayed, it's not that weird to imagine a scenario where the governments there are just totally won over by the prophets and they decide to not implant this technology at all. If you think about what happened to nuclear power in the 70s, in many different countries, maybe something similar could have happened to the Green Revolution. So it's important to beat the Prophet. Maybe that's not the correct way to say it. But one way you could put it is: It's important to beat the prophets before the policies are passed. You have to get a good bit of technology in there.Charles C. Mann   This is just my personal opinion, but you want to listen to the prophets about what the problems are. They're incredible at diagnosing problems, and very frequently, they're right about those things. The social issues about the Green Revolution… they were dead right, they were completely right. I don't know if you then adopt their solutions. It's a little bit like how I feel about my editors–– my editors will often point out problems and I almost never agree with their solutions. The fact is that Borlaug did develop this wheat that came into India, but it probably wouldn't have been nearly as successful if Swaminathan hadn't changed that wheat to make it more acceptable to the culture of India. That was one of the most important parts for me in this book. When I went to Tamil Nadu, I listened to this and I thought, “Oh! I never heard about this part where they took Mexican wheat, and they made it into Indian wheat.” You know, I don't even know if Borlaug ever knew or really grasped that they really had done that! By the way, a person for you to interview is Marci Baranski–– she's got a forthcoming book about the history of the Green Revolution and she sounds great. I'm really looking forward to reading it. So here's a plug for her.In Defense of Regulatory DelaysDwarkesh Patel   So if we applied that particular story to today, let's say that we had regulatory agencies like the FDA back then that were as powerful back then as they are now. Do you think it's possible that these new advances would have just dithered in some approval process that took years or decades to complete? If you just backtest our current process for implementing technological solutions, are you concerned that something like the green revolution could not have happened or that it would have taken way too long or something?Charles C. Mann   It's possible. Bureaucracies can always go rogue, and the government is faced with this kind of impossible problem. There's a current big political argument about whether former President Trump should have taken these top-secret documents to his house in Florida and done whatever he wanted to? Just for the moment, let's accept the argument that these were like super secret toxic documents and should not have been in a basement. Let's just say that's true. Whatever the President says is declassified is declassified. Let us say that's true.  Obviously, that would be bad. You would not want to have that kind of informal process because you can imagine all kinds of things–– you wouldn't want to have that kind of informal process in place. But nobody has ever imagined that you would do that because it's sort of nutty in that scenario.Now say you write a law and you create a bureaucracy for declassification and immediately add more delay, you make things harder, you add in the problems of the bureaucrats getting too much power, you know–– all the things that you do. So you have this problem with the government, which is that people occasionally do things that you would never imagine. It's completely screwy. So you put in regulatory mechanisms to stop them from doing that and that impedes everybody else. In the case of the FDA, it was founded in the 30 when some person produced this thing called elixir sulfonamides. They killed hundreds of people! It was a flat-out poison! And, you know, hundreds of people died. You think like who would do that? But somebody did that. So they created this entire review mechanism to make sure it never happened again, which introduced delay, and then something was solidified. Which they did start here because the people who invented that didn't even do the most cursory kind of check. So you have this constant problem. I'm sympathetic to the dilemma faced by the government here in which you either let through really bad things done by occasional people, or you screw up everything for everybody else. I was tracing it crudely, but I think you see the trade-off. So the question is, how well can you manage this trade-off? I would argue that sometimes it's well managed. It's kind of remarkable that we got vaccines produced by an entirely new mechanism, in record time, and they passed pretty rigorous safety reviews and were given to millions and millions and millions of people with very, very few negative effects. I mean, that's a real regulatory triumph there, right?So that would be the counter-example: you have this new thing that you can feed people and so forth. They let it through very quickly. On the other hand, you have things like genetically modified salmon and trees, which as far as I can tell, especially for the chestnuts, they've made extraordinary efforts to test. I'm sure that those are going to be in regulatory hell for years to come. *chuckles* You know, I just feel that there's this great problem. These flaws that you identified, I would like to back off and say that this is a problem sort of inherent to government. They're always protecting us against the edge case. The edge case sets the rules, and that ends up, unless you're very careful, making it very difficult for everybody else.Dwarkesh Patel   Yeah. And the vaccines are an interesting example here. Because one of the things you talked about in the book–– one of the possible solutions to climate change is that you can have some kind of geoengineering. Right? I think you mentioned in the book that as long as even one country tries this, then they can effectively (for relatively modest amounts of money), change the atmosphere. But then I look at the failure of every government to approve human challenge trials. This is something that seems like an obvious thing to do and we would have potentially saved hundreds of thousands of lives during COVID by speeding up the vaccine approval. So I wonder, maybe the international collaboration is strong enough that something like geoengineering actually couldn't happen because something like human challenge trials didn't happen.Geoengineering Charles C. Mann   So let me give a plug here for a fun novel by my friend, Neal Stephenson, called Termination Shock. Which is about some rich person just doing it. Just doing geoengineering. The fact is that it's actually not actually against the law to fire off rockets into the stratosphere. In his case, it's a giant gun that shoots shells full of sulfur into the upper atmosphere. So I guess the question is, what timescale do you think is appropriate for all this? I feel quite confident that there will be geoengineering trials within the next 10 years. Is that fast enough? That's a real judgment call. I think people like David Keith and the other advocates for geoengineering would have said it should have happened already and that it's way, way too slow. People who are super anxious about moral hazard and precautionary principles say that that's way, way too fast. So you have these different constituencies. It's hard for me to think off the top of my head of an example where these regulatory agencies have actually totally throttled something in a long-lasting way as opposed to delaying it for 10 years. I don't mean to imply that 10 years is nothing. But it's really killing off something. Is there an example you can think of?Dwarkesh Patel   Well, it's very dependent on where you think it would have been otherwise, like people say maybe it was just bound to be the state. Charles C. Mann   I think that was a very successful case of regulatory capture, in which the proponents of the technology successfully created this crazy…. One of the weird things I really wanted to explain about nuclear stuff is not actually in the book.

This week, please join authors John McMurray and David Cherney, editorialist Kausik Umanath, as well as Associate Editors Ian Neeland and Brendan Everett as they discuss the original research articles "Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights from DAPA-HF" and "Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition" and editorial ""Dip" in eGFR: Stay the Course With SGLT-2 Inhibition." Dr. Carolyn Lam: Welcome to Circulation On the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, Associate Editor from the National Heart Centre and Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, Associate Editor and director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, it's the season of double features. Except this time, we're having a forum discussion of two related articles and an editorial that discusses both. What is it on? SGLT2 inhibitors. In the first paper, an analysis from the DAPA-HF trial, looking specifically at that initial dip in GFR that follows initiation of dapagliflozin in patients with HFrEF. Then we will discuss further, in a mechanistic way, the renal and vascular effects of combining SGLT2 inhibition on top of ACE inhibition. Lots and lots of good learning and insights, but let's go on first to the other papers in today's issue. Shall we? Dr. Greg Hundley: You bet, Carolyn, and I'm going to grab a cup of coffee. Carolyn, in this issue, wow, so many exciting original articles. In fact, there are two more articles that were going to pair together, both clinical and pertaining to TAVR procedures. In the first one, it was a group of authors led by Dr. Duk-Woo Park from the Asan Medical Center at the University of Ulsan College of Medicine. They conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy or DAPT, aspirin plus clopidogrel, in patients who had undergone successful TAVR and did not have an indication for anticoagulation. Now in this study, Carolyn, the primary endpoint was an incidence of leaflet thrombosis on four-dimensional computed tomography, CT, performed at six months after the TAVR procedure. Key secondary endpoints were the number and volume of new cerebral lesions on brain magnetic resonance imaging or MRI and the serial changes of neurological and neurocognitive function between six months and that time immediately post the TAVR procedure. Dr. Carolyn Lam: Oh, interesting. What did they find? Dr. Greg Hundley: Right, Carolyn. In patients without an indication for long-term anticoagulation after successful TAVR, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effect on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the two groups. Now because the study was underpowered, the results should be considered really as hypothesis generating, but do highlight the need for further research. Dr. Greg Hundley: Carolyn, there's a second paper pertaining to transcatheter aortic valve prosthesis. It's led by a group directed by Dr. Paul Sorajja from the Minneapolis Heart Institute Foundation and Abbott Northwestern Hospital. Carolyn, these authors prospectively examined 565 patients with cardiac CT screening for HALT, or what we would define as hypoattenuating leaflet thickening, at 30 days following balloon-expandable and self-expanding TAVR. Now, deformation of the TAVR prosthesis, asymmetric prosthesis leaflet expansion, prosthesis sinus volumes, and commissural alignment were analyzed on the post-procedural CT. For descriptive purposes, an index of prosthesis deformation was calculated, with values greater than 1 representing relative midsegment underexpansion. A time-to-event model was also performed to evaluate the association of HALT with the clinical outcomes. Dr. Carolyn Lam: Oh, interesting. What did they find? Dr. Greg Hundley: Right, Carolyn. Nonuniform expansion of TAVR prosthesis resulting in frame deformation, asymmetric leaflet, and smaller neosinus volume was related to the occurrence of HALT in patients who underwent TAVR. What's the take home here, Carolyn? These data may have implications for both prosthesis valve design and deployment techniques to improve clinical outcomes in these patients. Now, Carolyn, both of these articles are accompanied by an editorial from Dr. Raj Makkar from the Smidt Heart Institute at Cedars-Sinai's Medical Center. It's a very lovely piece entitled Missing Pieces of the TAVR Subclinical Leaflet Thrombosis Puzzle. Well, how about we check what else is in this issue? My goodness, this was a packed issue. First, Carolyn, there are three letters to the editor from Professors Ennezat, Dweck, and then a response from Dr. Banovic pertaining to a follow-up from a previously published study, the AVATAR study, in evaluating valve replacement in asymptomatic aortic stenosis. There's also a Perspective piece from Dr. Wells entitled “Treatment of Chronic Hypertension in Pregnancy: Is It Time For A Change?” There's a Global Rounds piece from Professor Berwanger entitled “Cardiovascular Care in Brazil: Current Status, Challenges, and Opportunities.” Then there's also a Research Letter from Professor Eikelboom entitled “Rivaroxaban 2.5 mg Twice Daily Plus Aspirin Reduces Venous Thromboembolism in Patients With Chronic Atherosclerosis.” Dr. Carolyn Lam: There's another Research letter by Dr. Borlaug on longitudinal evolution of cardiac dysfunction in heart failure with normal natriuretic peptide levels. There's also a beautiful Cardiology News piece by Bridget Kuehn on the post-COVID return to play guidelines and how they're evolving. Well, that was a great summary of today's issue. Let's hop on to our feature forum. Shall we? Dr. Greg Hundley: You bet, Carolyn. Can't wait. Dr. Carolyn Lam: Today's feature discussion is actually a forum because we have two feature papers in today's issue. They all surround the cardiorenal interaction, should I say, of the SGLT2 inhibitors. For the first paper, discussing that initial decline or that dip in the GFR following initiation of dapagliflozin would be Dr. John McMurray, who's the corresponding author of this paper from DAPA-HF. Dr. John McMurray's from the University of Glasgow. Now next, we have also the corresponding author of another paper, really going into the mechanistic insights of the renal and vascular effects of combined SGLT2 and ACE inhibition. Dr. David Cherney is from Toronto General Hospital, University of Toronto. Dr. Carolyn Lam: We have the editorial list of these two wonderful papers, Dr. Kausik Umanath from Henry Ford Health in Michigan. Finally, our beloved associate editors, Dr. Ian Neeland from Case Western Reserve and Dr. Brendan Everett from Brigham and Women's Hospital, Harvard Medical School. Thank you, gentlemen. Now with all of that, what an exciting forum we have in front of us. Could I start by asking, of course, the respective authors to talk a little bit about your papers? I think a good place to start would be with Dr. McMurray. John, please. Dr. John McMurray: Thanks, Carolyn. I think our paper had three key messages. The early dip in eGFR that we saw was, on average, very small in patients with heart failure, about 3 mLs/min or about 5%. Very few patients had a large reduction in the eGFR. It was around 3%. Dapagliflozin-treated patients had a 30% or greater decline compared to about 1% of placebo patients. Finally, very few of those patients had a decline in the eGFR below a critical threshold, which for cardiologists might be around 20 mLs/min. We saw that in only five patients; that's 0.2% of the dapagliflozin-treated patients. Second message was that that early decline partially reverses. The nadir in our study was about 14 days. But by 60 days, on average, eGFR had increased again. Hold your nerve if you see an early decline in eGFR.   Dr. John McMurray: Maybe the most important message was that that decline in the eGFR is not associated with worse cardiovascular or renal outcomes. In fact, if anything, the opposite. If you look at the patients in the dapagliflozin group with a 10% or greater decline in eGFR, then compare it to patients who didn't have that decline, these individuals were about 27% less likely to experience the primary composite outcome of worsening heart failure and cardiovascular death. If you look at the placebo group, we saw exactly the opposite. Amongst those who had a greater than 10% decline in eGFR compared to those who didn't, those people with the early decline in eGFR were 45% more likely to experience the primary composite endpoint. The same is true for other cardiovascular outcomes for worsening kidney function. In the dapagliflozin group, decline in eGFR was not associated with more adverse events, not associated with more treatment discontinuation. That small decline in the eGFR is not a bad prognostic sign. If anything, it might be the opposite. Dr. Carolyn Lam: Thank you so much. That was really clear. David, are you going to tell us why this decline occurs? Dr. David Cherney: Yeah. Perhaps the paper that we published gives some insights into the mechanisms that are responsible for some of those changes in GFR that are thought to be acute hemodynamic effects. In the between trial, which is the trial that we published examining the effect of ACE inhibition followed by SGLT2 inhibition in patients with type 1 diabetes, we also saw that there was an expected effect of adding SGLT2 inhibition on top of an ACE inhibitor in people with uncomplicated type 1 diabetes. This acute dip in GFR was seen in this cohort of patients. We included only 30 patients in this small mechanistic study. At the same time, along with that dip in GFR, we also saw an increase in measures of proximal natriuresis. That proximal sodium loss is linked with changes in sodium handling in the kidney, which then causes changes in both probably afferent and efferent tone, which causes this dip in GFR primarily through natriuresis in this phenomenon called tubuloglomerular feedback. That was one major observation that gives insight into what we see in larger trials around the dip in GFR. Dr. David Cherney: In our mechanistic study, we also saw an additive effect on blood pressure. Blood pressure went down further with the addition of empagliflozin on top of an ACE inhibitor. In terms of the mechanisms that are responsible for the reduction in blood pressure, natriuresis certainly may be in part responsible, but we also saw a novel observation whereby there was a reduction in peripheral vascular resistance using noninvasive measures. There are likely several mechanisms that are responsible for the reduction in blood pressure. Then finally, we also saw reductions in markers of oxidative stress, which may also account for some of the effects that we see in blood pressure, as well as potentially some of the anti-inflammatory and anti-fibrotic effects that we see at least in experimental models that may have some clinical translatability to humans as well around the clinical benefits. I think the blood pressure, the renal hemodynamic effects, and some of the neurohormonal mechanisms are the major observations that we saw that may in part explain some of the really nice changes that were seen in Dr. McMurray's study. Dr. Carolyn Lam: Right. Thanks, David. But these were patients with type 1 diabetes and no heart failure. John, do you have any reflections or questions about how that may apply? By the way, what a beautiful study. Thank you, David. Dr. David Cherney: Pleasure. Thank you. Dr. John McMurray: Yes, David. I really enjoyed your study. In fact, I think, Carolyn, it does shed some insights perhaps to what's going on. As David pointed out, the reduction in peripheral arterial resistance, reduction in blood pressure, that may play some role in that early dip in eGFR as well as autoregulation in the kidney. Then the other interesting thing is that the distal nephron seems to adapt to that effect in the proximal tubule. Again, that may account for some of that recovery in eGFR, that reversal in the early dip that I spoke about, and which I think is very clinically important because, of course, physicians should make sure that they recheck eGFR if they see that early dip. Because they may find that few weeks later that that dip is much smaller and of much less concern. Dr. Carolyn Lam: Thank you, John. In fact, you're saying, stay the course, right- Dr. John McMurray: I have. Dr. Carolyn Lam: ... with the SGLT2 inhibitors. I'm actually stealing the words of the title of the editorial, a beautiful editorial by Kausik. I love that. Stay the course. Kausik, please, could you frame both papers and then with an important clinical take home message for our audience? Dr. Kausik Umanath: Sure. I think the analysis by John and his group was really relevant with the large sample size. What's impressive? Similar to a lot of these other SGLT2 studies that have come out, both in heart failure and in kidney disease progression and so on, it's remarkable how the other analysis, like the analysis of EMPA-REG and CREDENCE and so on, of similar dips. All show more or less the same magnitude, the same relative proportions of this GFR trajectory. I think the mechanistic study only highlights that though it's working with a slightly different population of type 1 patients and much earlier in their course in terms of where their GFRs are. Dr. Kausik Umanath: The other piece is that ultimately we need to understand this dip and know to monitor for it and so on. But I think the general clinician should really understand that a dip of greater than 10% really occurs in less than half the population that takes these agents. That dip, if it occurs, certainly doesn't do any harm. That said, if they see a bigger dip in the 30% range, monitor more closely and consider making sure that there aren't any other renal issues out there for that patient because they are a much smaller proportion of patients in these large trials that generate that level of dip. They should be monitored. Dr. Kausik Umanath: The other thought that we had, and thinking through this in a practical sense, is because you expect this dip, many of our cardiologists or even the nephrologists when we titrate these drugs, they're on a suite of other drugs. It's probably best to not adjust their Lasix or their loop diuretic, or their RAAS inhibitor at the same time as you're adjusting the SGLT2 inhibitor or starting it because then you may just introduce more noise into the GFR changes that you see over the next several weeks. It may be a sequential piece or at least holding those other agents constant while this gets titrated and introduced is a prudent course of action, so you don't misattribute changes. Dr. Carolyn Lam: Thanks so much. What clinically relevant points. In fact, that point about the diuretic especially applies in our heart failure world. You see the dip. Well, first, make sure the patient's not overdiuresed. Remember, there's more that the patient's taking. Thank you. That was a really great point. Brendan and Ian, I have to get you guys to share your views and questions right now. But before that, can I take a pause with you and just say, aren't you just so proud to be AEs of Circulation when we see papers like these and we just realize how incredible the data are and the clinical implications are? I just really had to say that. All right. But with that, please, what are your thoughts, Brendan? Dr. Brendan Everett: Yeah, sure. Thank you, Carolyn. Hats off to all three of our authors today for doing some amazing science. Thank you for sending it to Circulation. I think, in particular, I handled David's paper. I'm not a nephrologist and I'm probably the furthest thing from a nephrologist. Had to do my best to try and understand these concepts that I'm not sure I ever even was exposed to in medical school many years ago. I think it shows the breadth of the interest in our readership. The fact that these changes in eGFR have become a primary focus for our cardiovascular patients and that the clinical implications are really important. I guess my question, David, is... In your paper, you talked a little bit about this hypothesis of hyperfiltration and the role that hyperfiltration plays in setting patients with diabetes up for kidney disease. Is that playing a role in John's observation or not? Again, as a non-nephrologist, I have trouble connecting the dots in terms of that hypothesis and John's observation of the clinical benefit for patients that have a reduction in eGFR as opposed to no change. Dr. David Cherney: Yeah. It's a great question. It's very difficult to know with certainty in a human cohort because we can't measure the critical parameter, which is intraglomerular pressure, which we think these changes in GFR are a surrogate for. But if we go along with that train of thought, along reductions in glomerular hypertension, it very much makes sense that the patients who dip are those who have the... They're taking their medication, number one. Number two, they respond physiologically in the way that you expect them to, which is that their GFR dips at least transiently and then goes back up again through some of the compensatory mechanisms that John mentioned earlier. As was mentioned not only in this paper, but also in previous analyses from CREDENCE and previous analyses from VERTIS CV and others have shown that indeed that dip in GFR is linked with longer term renal benefits, at least. That is reflected in a reduction in the loss of kidney function over time. Dr. David Cherney: The patients who are on an SGLT2 inhibitor and those who dip by around 10% or less, those patients tend to do the best over time in terms of preserving GFR, not losing kidney function compared to patients who are on an SGLT2 inhibitor but do not dip, or those patients who actually have an increase in GFR. That is consistent with this idea that there may be a reduction in glomerular pressure, which is protective over the long term. That ties back into your question around hyperfiltration that this may indeed be due to a reduction in glomerular pressure, which is linked with risk over the long term. Dr. Carolyn Lam: Ian? Dr. Ian Neeland: I wanted to echo Brendan's comments about the excellent science. When I read these papers, it really speaks to the existential struggle that cardiologists have between kidney function and these medications that we know have cardiovascular benefits. How do we manage that practically? It's so clinically relevant, both the observation that John's paper made about the dip in the DAPA-HF trial as well as, David, your mechanistic insights. Dr. Ian Neeland: I wanted to ask John potentially about the most fascinating aspect to me of this paper was that patients with a dip of 10% or more actually ended up doing better in terms of cardiovascular outcomes, specifically hospital heart failure and hospitalizations than people on placebo with a greater than 10% dip. It speaks to the fact that... Is the physiology going on here different between those individuals whose GFR went down on placebo versus those who are on SGLT2 inhibitors? All the mechanistic insight that David's paper had in terms of blood pressure and intraglomerular pressure, how does that feedback and speak to why heart failure is strongly linked to this mechanism? We see this not just with SGLT2 inhibitors, but there are other medications now coming out showing that there's a relationship between this dip in GFR and heart failure. Can you speak to why this heart failure-kidney connection is so important and becoming greater and greater in terms of our understanding? Dr. John McMurray: Well, thank you for asking me the hardest question and one that I truly don't think I have a good answer to. I think it's obvious to all of us that the kidney is central in heart failure and perhaps cardiologists have neglected that fact, focusing more on the other organ. But by definition, almost the fluid retention that characterizes heart failure in terms of signs, and probably is the primary cause of symptoms, that clearly is a renally-mediated phenomenon. The kidney must be central to all of this. I think David right. I think the decline in eGFR that you see with this drug is simply a marker that the drug is having its physiological effect or effects. Whatever those are, they're beneficial. Clearly, patients who have an eGFR decline on placebo are different and they reflect, again, the patients that we see all the time. As our patients with heart failure deteriorate, one of the things that we commonly see, in fact becomes one of the biggest problems that we have to deal with, is that their kidney function declines. As their symptoms get worse, as their cardiac function gets worse, their kidney function also declines. Dr. John McMurray: I think you're seeing two contrasting effects here. One is the background change in eGFR, which is the placebo patients, and we've always known that that's a bad thing. Then we're seeing that early within 14 days marker of the pharmacological or physiological action of the drug. I hope you don't ask me how SGLT2 inhibitors work in heart failure. That's the other most difficult question I can think of, but I think this is just a marker of the fact that they are working. Dr. David Cherney: Yeah. Just to add to that briefly, there is this difficulty in sorting out the mechanisms that are relevant around the acute effects in the kidney that the dip in GFR reflects natriuresis that could keep patients out of heart failure; that the reduction in glomerular pressure reduces albuminuria. Albuminuria reduction is linked with kidney protection. It's linked with heart failure and ASCVD protection. Then there's also this concept of if you dip and then you stay stable afterwards, your GFR stays stable afterwards, those patients with stable kidney function that's not declining, the dippers in other words, those patients are probably able to maintain salt and water homeostasis better than someone who's declining more rapidly. All these things probably tie together in order to reflect, of course, there's a renal protective effect, but that some of those mechanisms may also tie into the heart failure mechanisms that John was mentioning. Dr. John McMurray: But, David, it's hard to imagine if we don't protect the kidney, we won't protect patients with heart failure given how fundamental, as I said, the kidney is, and how fundamentally important worsening kidney function is. Not only because it is a marker of things going badly, but also because it often results in discontinuation or reduction in dose of other life-saving treatments. To Kausik's point, it was very important about the risk of changing background life-saving disease modifying therapy. Actually, we didn't see that in DAPA-HF, which was very intriguing. There was no reduction in use of renin-angiotensin system blockers or mineralocorticoid receptor antagonists. Dr. Carolyn Lam: Thank you so much, gentlemen. Unfortunately, we are running out of time, but I would really like to ask one last question to the guests, if possible. Where do you think the field is heading? What next? What's the next most important thing we need to know? David, do you want to start? Then John, then Kausik. Dr. David Cherney: I think one of the aspects that we need to know in the future is where else can we extend these therapies into novel indications and extend the boundaries of where we currently work with these therapies. People with type 1 diabetes, for example, with either heart failure or with significant kidney disease, patients with kidney transplantation, is there a renal or cardiovascular protective effect? Then another high risk cohorts who have not been included in trials, those on immunosuppressants, for example, who were excluded from the trials. I think those are some of the areas that we need to extend into now that we understand how these therapies work in even very sick patients and that we also know that they likely have at least some benefit through suppressing inflammation, and possibly reducing infectious risks. That would provide a rationale for extending into some of these new areas. I think that's certainly, hopefully on the horizon for us. Dr. Carolyn Lam: John? Dr. John McMurray: Carolyn, obviously I think looking at post myocardial infarction population, that's an obvious place to go. There are a couple of trials there. I suppose the trial that I would love to see, and which I think would address the core question that we've been discussing today, which is: Is this all about the effect in the kidney and how important is the diuretic and natriuretic action of these drugs in heart failure? I think the key study that would address this would be doing a study in patients on dialysis. Because in those patients we could, I think, separate the issue of natriuresis, diuresis, and maybe even the dip in EGR that we've been talking about. If these drugs prove to be effective in end-stage kidney disease, patients on dialysis, that would be really fascinating. Dr. Carolyn Lam: Kausik? Dr. Kausik Umanath: That is a very interesting point. I don't know that we know necessarily outcomes, but I think from working with the DAPA-CKD, we do have a little bit of the safety data because we did continue it. I was the US MLI for that study and we did continue the SGLT2 passed into renal failure. There is a little bit of safety data there. But I don't think once you've declared an outcome, you're not collecting outcomes data after that point. That's a very interesting area to look into. Dr. Kausik Umanath: I also think the other place where this field's heading is trying to better tier and layer the multitude of agents. I think we've been waiting for about 20 to 30 years, at least in the kidney field, for something new to affect the progression of kidney disease after the ACE/ARB trials and so on. This one we've got SGLT2 inhibitors. We've got the new MRA, finerenone, and so on, which also have very beneficial cardiovascular effects. The question becomes: How do we layer these therapies? Which sequence to go in? Some of the others that are in pipeline as well that are out there that have very beneficial cardiovascular effects that may indeed also help kidney function and diabetes control, which do you go with first and so on? Dr. Carolyn Lam: Wow! Thank you so much. We really could go on forever on this topic, but it has been tremendous. Thank you once again. On behalf of Brendan, Ian, Greg, thank you so much for joining us today in the audience. You've been listening to Circulation On the Run. Don't forget to tune in again next week. Dr. Greg Hundley: This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Hello Interactors,We’re staying in Russia this week because the United States sticks with Russia. At least they used to. And boy did they need it. The famines that have swept through that region over the years have taken the lives of tens of millions of people. Even though Russia was home to the world’s leading seed expert. But the U.S. was always there to bail them out. If the U.S. fell into a food crisis, would Russia return the favor?As interactors, you’re special individuals self-selected to be a part of an evolutionary journey. You’re also members of an attentive community so I welcome your participation.Please leave your comments below or email me directly.Now let’s go…SEEDS OF CHANGE YIELDS DEEDS OF THE DERANGEDJoseph Stalin liked Trofim Lysenko. He grew up poor far away from Moscow just like him. Stalin was from Georgia and Lysenko Ukraine. Both identified as proletariats. They despised the bourgeoisie imperialistic West. Including highly educated and trained scientists. Lysenko was a horticulturist, studied agricultural, and then worked in the department of physiology at the Ukrainian Genetics Laboratory. But he wasn’t like other scientists. He devised his own homegrown, unproven experiments. He invented theories with pseudo-scientific names like “jarovization” or “vernalization” from Latin’s ‘vernum’ or spring. His claims became known as “Lysenkoism.” Other Russian scientists looked the other way. Russia’s most respected biologist, geneticist, and geographer, Nikolai Vavilov, thought Stalin’s new friend was a crackpot. It wouldn’t end well.Lysenko got lucky with ‘vernalization’. He tricked wheat seeds into blooming early by treating them with moisture in cold temperatures as a way to produce yields in the spring. The trick had already been performed by American John Hancock Klippart in 1857, but Lysenko gave it a name. He also believed the deceived seeds from these plants would magically inherit the ability to do the same on their own. His theory ran counter to empirical evidence and to the knowledge and experience of Vavilov. Vavilov worried Lysenko’s tricks, unproven theories, and over promises to Stalin and the Soviet government could lead to catastrophic errors and the worsening of the routine famines Russia was trying to escape.But Stalin embraced Lysenko’s folksy and unorthodox ways. He believed in his salt-of-the-earth intuition and grew suspicious of the world-renowned and respected science of Nikolai Vavilov. Vavilov was the winner of the Lenin Prize, one of the most prestigious awards in science, and was respected worldwide. He traveled the globe successfully identifying the geographic genetic origins of cultivated plants. He guest-lectured and rubbed elbows with those Western imperialists Stalin despised. Vavilov also spoke poorly of the former Ukrainian peasant come pseudo-scientist Stalin had grown fond of.In 1936 Stalin replaced Vavilov with Lysenko as the head of the Soviet Academy of Agriculture. Six years later, in 1941, Stalin sentenced Vavilov to execution on claims he was trying sabotage Stalin’s agricultural plans. His sentence was then reduced to a prison term. Vavilov, who grew up fearful of starvation in a village prone to crop failures and food rationing – a scientist who dedicated his life to eradicating famine – died in prison in 1943 of starvation. Famines had been ravishing Russia for a century already. The large-scale farm practices of today started in the nineteenth and twentieth centuries. But missteps led to widespread famine, displacement, and environmental damage. Technological advancements allowed expansive grasslands to be converted to cropland around the world, including Russia, Australia, Argentina, South Africa, Canada, and the United States. An explosion of European immigrants to the United States in the mid 1800s, together with The Homestead Act of 1862, pushed immigrants into prairies to the West and North. Some ventured into Canada. The Civil War ended in 1865 and four years later the Transcontinental Railroad was completed. Both increased the number of agrarian colonizers to the Great Plains.But the climatic patterns in these areas played a role in the evolution of these plains. The grasslands are arid with periods of intense rainfall followed by drought. Settlers could be deceived into believing these rainfalls were routine only to witness periods of extreme drought. Farmers in the 1870s and 1880s witnessed regular rainfall only to see it disappear in the 1890s. Instead of consulting with Indigenous farmers on how they farmed the land for millennia, the colonists instead expanded area croplands and intensity to make up for short yields. Some used the land to graze cattle leading to even more elimination of the natural grasses needed to nourish and sustain the soil. The U.S. government accelerated farm expansion by altering the Homestead Act to include larger plots of land. The rain returned in the 1920s which attracted another wave of farmers. Farmland in a section of northwestern Texas and eastern New Mexico doubled in the two decades between 1900 and 1920 and tripled in just five years between 1925 and 1930.  Russia saw similar expansions of large-scale agriculture. In the late 1800s and early 1900s, groundbreaking research by soil scientist and geographer Vasilii Dokuchaev, the father of soil science, revealed for the first time the role climate and topography play in soil health. He went on to develop the world’s first soil classification system. Some farmers, including immigrant German Mennonites, adopted drought tolerant farming practices Dokuchaev recommended.Meanwhile, most of Russia, like the United States, continued large-scale overly intensive farming techniques – though Russia lagged in mechanization. Both the United States and Russia, set on expansion, growth, and domination, gambled with the climate, soil, plants, and the crops they yielded. They ignored both emerging science and age-old sustainable practice that likely would have mitigated inevitable crop failure, famine, and long-lasting and long-ranging environmental and social devastation. Destruction so severe they compounded the effects of natural disasters.Between 1921 and 1923 extreme droughts and winters led to plant disease, insect infestation, and soil erosion throughout the converted grasslands of Russia, Ukraine, and surrounding regions. Famine ensued causing millions to die of starvation. Ravaged by WWI and the Russian Civil War, the Soviet government, then under Vladimir Lenin, was forced to import food and organize relief efforts. In 1921 Lenin called on the United States to help. The American Relief Administration, headed by future President Herbert Hoover, employed 300 Americans and a 120,000 Russians to provide relief. It was an extension to European relief from WWI. They provided daily meals for over 10.5 million people while also administering medical aid to typhus sufferers – a feverish epidemic claiming even more Russian lives.GO GREENThe relief from America worked. By 1923 the Soviet government was able to stockpile enough grain to organize their own relief efforts and the U.S. stepped away. But Russia continued to be hit with episodes of drought. In 1924 another wave hit and the Soviets were once again forced to organize relief efforts. Again, they stockpiled enough to make it through 1925 and 1926 only to be hit again in 1928. Convinced traditional farming techniques were unsustainable, the Soviet government initiated programs that mimicked industrialized farming techniques in the United States.Another drought came in 1931 and 1932 and with it more famine. Joseph Stalin had risen to power amidst the Russian Revolution. Unlike Lenin, he refused support from the outside. By 1933, when food stocks began to rise again four million more people had died from famine. But the United States would have been in no position to help this time anyway. In 1930, widespread drought spread through the Great Plains stretching from Canada to Mexico. The natural grasses that once protected soil from blowing away had either been tilled for crops or consumed by cattle. The Industrial Age had given way to industrial farming. A substantial gamble with colossal consequences. The Dust Bowl, or Dirty Thirties, a natural disaster compounded by poor agricultural practices and imperialist hubris, impacted over 100 million acres. It intensified the Great Depression. If the dust storms didn’t destroy homes and farms, failed mortgages and loans did. Between 1930 and 1940 nearly 3.5 million people evacuated the lands they had only recently colonized and practically destroyed. Including their native inhabitants.Meanwhile, back in Russia, Stalin made another gamble in 1936. He bet on “Lysenkoism”. He believed it would solve the Soviet agricultural malaise sending the one man capable of potentially solving the region’s, maybe the world’s, agricultural problems to starve to death – Nikolai Vavilov. But soon came WWII and more geopolitical disruption in a Soviet Union still trying to figure itself out. And then, in 1946 and 1947, another Russian famine emerged. Again, Stalin refused aid and two million more died of starvation.But little did Stalin know, many of the scientists that worked under Vavilov had hidden his seed collection and continued to conduct experiments in private. One esteemed plant breeder, Pavel Luk’ianenko, drafted off the work of Vavilov and bred a variety of semi-dwarf wheat seeds in 1950 that would change the course of Russian agriculture forever. By the time of his death in 1972 he was credited with breeding or co-breeding 15 different varieties of regionalized winter wheat seeds.            His work was Russia’s contribution to a larger global Green Revolution, a systematic and coordinated effort in the 1950s and 1960s between genetically modified seed breeding, chemical fertilizers, land use policy, public and private capital, and mechanized technology that massively increased crop yields. The American scientist and Nobel Prize winner credited with birthing this revolution, Norman Borlaug, said in 2000 that “Had the global cereal yields of 1950 still prevailed in 1999, we would have needed nearly 1.8 billion hectares of additional land of the same quality – instead of the 600 million that was used – to equal the current global harvest".After Stalin’s death in 1953, Nikita Khrushchev rose to power. Khrushchev was Russian but had ruled Ukraine for a decade. He witnessed struggling farmers endure famine and invented what he called “agro-towns” – small villages in remote rural areas with a library and stores where farmers could live and be better supported. But during the drought of 1946, he had to beg Stalin for aid after over-estimating Ukrainian crop yields. It was a fissure that cost him his post in Ukraine. However, his dismissal led to a position in Moscow closer to Stalin that surely cemented his rise to power seven years later.One of Khrushchev’s first programs was “Virgin Lands”. He proposed the conversion of 25 million hectares of arid grasslands to croplands in Siberia and Kazakhstan. Within a year this region became a significant contributor to Soviet grain yields. But they soon diminished and in 1962 and 1963 came another drought. In an echo of the Dust Bowl, winds picked up and blew away most of the topsoil that had previously been secured by grassland. Again, a massive shortfall of wheat forced Khrushchev to seek foreign aid. Ten million tons of grain were imported from Canada and the United States. Quantities of this magnitude were likely the result of the crop yield successes of the Green Revolution. But they were also making up for the environmental failings of the Green Revolution.NUT JOBIt can be hard accepting curses that can come with blessings. Such is the damaging and delicious duality of modern agriculture. We can’t seem to live with it, and we don’t dare try to live without it. But we do have a choice over how large-scale agriculture is implemented. This is unlike the effects of climate change where we can’t live with them, and we don’t have a choice to live with out them. These historical environmental extremes that plagued the former Soviet agricultural lands continue to this day. In 2009, Russia was on course to export record amounts of grain. Then, in 2010, a wildfire brought on by severe drought turned acres of golden grain to ash. Vladimir Putin was forced to cancel exports. And like those before him, was forced to import food to stave off widespread famine.Russia, Ukraine, Kazakhstan, and other surrounding countries continue to adjust to extreme weather patterns. Still, much of that ‘Virgin Land’ once converted to cropland over the past 50-60 years has been abandoned due to soil depletion brought on by large-scale intensive factory farming. Just a small fraction of the original ‘Virgin Lands’ are farmed in Kazakhstan today. But they continue to learn and adjust…as we all must.The effects of climate change are global in scale, but differ in variety, intensity, and regularity at a regional and local level. So does the impact on people and place. As a result, responses to these effects must also differ in variety, intensity, and regularity. But intent matters. I’m convinced scientists like Vavilov, Lysenko, Luk’ianenko, and Borlaug were intent on saving people from starvation. They all witnessed firsthand real suffering of starving individuals and the loss of entire populations.But I’m less convinced of the intentions of politicians like Stalin and Putin. I’m also skeptical of the intentions of Western coalitions backed by corporations who prioritize capital, political control, and short-term quarterly earnings. They seem more intent on feeding growing GDP figures than the starving figures of the emaciated. Stuff pockets of greed over hungry mouths to feed. Let the soils blow away, so long as the board boosts my pay. Shrink operating expenditures amidst rising temperatures. Large-scale government schemes feed delusional utopian dreams. Avoid political disruption by funding criminal corruption. Intention matters.As an example, in 1947 the British Government wanted to increase peanut production to sell as oil on the world market. So, together with Unilever, then went to the East Africa territory of Tanganyika to convert the wooded plains to peanut farms. An area England had militarily occupied since 1916. No one involved in the project bothered to study the soil and topography. They had to remove Mvule trees to make way for croplands, but they didn’t account for their deep, stubborn, thirsty roots. Their tractors were ruined in the process. New tractors damaged the soil with their weight. Their engines were too weak to churn the hard soils. In two years, they had only cultivated 16% of what they had planned. By 1951 the British government called it quits. They had spent six times the value of the crops they had grown. The director of the program was a former Russian who applied techniques of his communist past. Leaders at Unilever demanded immediate results to fit their revenue goals. Both of their approaches were insensitive to local people and place leaving it ravaged as they wrote off the loss and flew away amidst the arid soil they had unearthed. They abandoned the people and place most impacted by their imperialistic Groundnut Scheme.A railroad was constructed to ship the elusive nuts to a harbor the British had built so they could float nut oil around the world. The port remains, but the rail was dismantled. The global transportation network is what allows those locally impacted by natural disasters to receive aid. Parts of Africa continue to be cut off from these networks. But it were not for these networks, millions more would have died of starvation over the past 200 years. The U.S. and Ukraine blame Russia for clogging those very networks today. Meanwhile, Putin blames the West for blocking fertilizer and grain imports into Russia. Both are true. And it’s also true that Russian wheat exports were up 80% in April over last year and rose 27% in May. They just may be the winner in Wheat sales this year, unless another drought hits and the fields turn to fire. But if Russia was hit with a famine inducing drought, would Putin ask Ukraine and the West for relief? Would America offer relief? What if America is hit with a famine inducing drought? Would China and Russia come to our aid?On June 27th, President Biden and members of the G-7 met in Austria to discuss a plan to massively invest in infrastructure throughout the developing world. They aim to thwart nonmembers like China and Russia from introducing future disruptions by controlling more infrastructure, like transportation. It’s a response to China’s Belt and Road Initiative. Biden said, “This isn’t aid or charity, it’s a chance for us to share our positive vision for the future…because when democracies demonstrate what we can do, all that we have to offer, I have no doubt that we will win the competition.” That hubris reminds me of the British Groundnut Scheme. Will the West be applying lessons learned from the devastating and deleterious effects of centuries of colonization? Are leaders any more sensitive to the needs and desires of the local people and places these schemes are sure to impact? These investments are long overdue, and China has a head start, but they must be done with the right intentions.Lack of adequate adoption of agricultural practice and needed infrastructure is what leaves regions most vulnerable to the negative agricultural effects of climate change. The way our food is produced, distributed, and sold heavily relies on transportation networks. The millions of people who were saved from starvation in the former Soviet Union is testimony to this fact. But responses also require acknowledgment, understanding, and support of local people and place…and their governments. Whether they share a common vision with the West or not.People situated in their places possess the necessary local and practical knowledge and ingenuity needed to augment the abundance of science that rests on centuries of historical successes and failures. Capital investment from the West is needed and necessary, but not sufficient or welcomed should the intent be to strengthen power, bolster profits, and exploit people and land. In other words, to repeat history. To learn the lesson, past sins must not be repeated. Instead of killing people, animals, and plants in the interest of political ideology, we should seek their engagement and invest in their ecology. In the words of Nikolai Vavilov in 1932, nine years before Stalin issued his execution sentence: “Many historical problems can be understood only because of the interaction between man, animals and plants.” This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit interplace.io

#GeekingOutSeries/Safety101/ChemicalsinFood/1This post is part of the Geeking Out series which presents data-driven information on food and farming, safety in the kitchen, practical science for cooks, cooking techniques and processes and other relevant nerdy stuff that every cook should know.  For the next few weeks, we will be covering topics from the chapter, Safety 101. This is the first of four parts.While the idea of pathogens posing a danger to our health is established knowledge-- we’ve all learned about it in elementary science for one, my reference to many chemicals that are in our food system as “poison” may raise some eyebrows.  I’m referring to three kinds: toxic chemicals that go on our crops such as fertilizers, herbicides, pesticides; are present in our meat and poultry like steroids and antibiotics, and are in ultra processed foods like sugar additives and preservatives. While there’s a growing body of woke citizens, health professionals, scientists, environmental groups and even government agencies like the CDC that acknowledge the toxicity in our food production system, most Americans don’t realize the gravity of the situation for a number of reasons.It’s fairly new. Widespread chemical use in agribusiness is relatively recent, gaining traction only in the mid twentieth century.  The adverse effects caused by chemical fertilizers and additives in our food were not easily identified or immediately apparent, sometimes taking years to diagnose. It’s only in the last decade there’s been broad consensus that sugars, particularly high fructose corn syrup, are linked to obesity, type 2 diabetes, heart disease and cancer.      Corporate greed.  The main reason for the use of chemicals in our food system is to increase efficiency and lower production costs (but not environmental and public health costs), which means bigger profits for companies. Big Business loves its bottom line and will do anything to protect it. Large amounts of money are spent trying to convince the public their products are great or that studies showing harmful effects are conflated. Sound familiar?  We’ve been down this road before with the tobacco industry denying for decades that smoking cigarettes causes cancer. Human nature.  Our tendency towards the path of least resistance means it’s easier not to change old habits or question previously established beliefs, despite growing available data that should convince us otherwise.  Plus, it’s not easy keeping up with food trends --margarine was in, now it’s out; wine was out, now in; coffee is…what now? It doesn’t help we’re bombarded with billions of dollars in unhealthy food advertising, brainwashing us since we were children. Sorting through the muck of false or misleading information is overwhelming.  To top it all, we’re not hardwired to be on red alert if we think the danger posed is far away.  Unlike e coli which could make you sick right away, toxic chemicals in our food system are a slow poison and it’s easy to believe we’re okay until we’re not.  Just like a lobster unaware it’s slowly boiling to death (also a good metaphor for why we’re not all panicking about global warming).Knowledge is key.  Stories can put things in perspective and convince us to take action. I hope that understanding how and why America’s food system is in crisis might be the nudge we all need to make food choices that benefit the planet and ourselves, and not just Big Business.Chemical Fertilizers, Herbicides and PesticidesIt’s impossible to overemphasize the danger posed by many chemicals in our food system.  They are not only toxic to us, but to other animals, the soil, the environment. Why the US is able to legally serve its populace harmful food comes down to corporate greed, how big money can influence government regulations, and insidious marketing that’s shaped culture and tastes predisposed to unhealthy food that keeps corporate coffers full.  For a detailed understanding of America’s food system from production to consumption,  I will defer to a few books that have strongly influenced me over the years:  Fast Food Nation by Eric Schlosser, Third Plate by Dan Barber and Micheal Pollan’s  Omnivore’s Dilemma and Cooked: A Natural History of Transformation.Monoculture America:  An OverviewMost commercial farming practices monoculture, the cultivation of a single crop in an area.  Think of those sweeping fields of Idaho corn or row after row of potatoes.  It’s ubiquitous and you could be forgiven for thinking this is how farming always was.  But that’s not right.  American Indians and other farmers practiced polyculture, planting diverse crops which were mutually beneficial not only to each other, but to maintaining and building soil health. The Three Sisters of Native American agriculture is one such well-known companion planting of corn, beans and squash. Jo Robinson in her book, Eating on the Wild Side describes:‘The Wyandot people, renamed Hurons by the French were masters of this art.  Each spring, the Wyandot women would walk to a cleared field and spread a mound of fish waste every three or four feet.  They covered the fish with dirt and then planted a few corn seeds in the center of each mound. When the corn leaves reached hand height, they planted beans next to the corn, then sprinkled pumpkin seeds between the mounds. The corn stalks grew tall and sturdy, providing support for the limply twining beans.  The beans made their contribution by drawing nitrogen dioxide out of the air and converting it to a stable form of nitrogen that could be used by all three plants, but especially by the nitrogen-hungry corn.  The broad squash leaves fanned out beneath the corn and beans, preventing weeds from growing, cooling the soil, and slowing the evaporation of water.”The function of the beans to draw out nitrogen dioxide from the air and convert it into a kind of nitrogen plants can use (ammonia and nitrate) is what’s called nitrogen-fixing.  Legumes, clover, lupines are some of the nitrogen-fixers commonly used to replenish the soil.  Another popular companion planting example is the home gardener’s tomatoes-basil combination.  According to the Farmer’s Almanac, not only do they taste good together, but the basil helps increase tomato yield and repels pests like mosquitoes, flies and aphids.In companion planting, not only is there a symbiotic relationship between plants, but the diversity provides insurance of crop survival. Blight might take down corn, but maybe the squash will survive. And when planting is diverse, it’s harder for pests to home in on their favorite food. Vast swaths of single crops are an all-you-can eat buffet waiting to happen.But in the 20th century, a confluence of events propelled America and much of the world’s agriculture into a monoculture landscape dependent on chemical fertilizers, pesticides and herbicides.     In 1909, A German chemist named Fritz Haber discovered a chemical way of “fixing” nitrogen, which is to produce liquid ammonia, the raw material for making nitrogen fertilizer. By 1913, the Haber-Bosch process was used to produce liquid fertilizers in greater quantities and by the time World War II was over, munitions factories which used ammonium nitrate for explosives, could find a new lease in life producing chemical fertilizers, thereby increasing supply and lowering costs to farmers.In the mid-50’s, another scientist, Norman Borlaug bred a variety of dwarf wheat that tripled yield with the use of fertilizers.  The wheat variety, regimen of fertilizers and single crop cultivation (monoculture) were tested in Mexico and then later in India, which was on the brink of a famine. With the template for breeding high-yield crops dependent on fertilizers a huge success, The Green Revolution of the 60’s was born and exported to many parts of the world, including the Philippines, where “miracle” rice, another fast yielding crop, was developed. And this is how monoculture agriculture dependent on chemicals became the norm in American Agriculture.The Ravages of Monoculture AgricultureThe Green Revolution had noble intentions and was a miracle with its bountiful yields, earning Borlaug the 1970 Nobel Peace Prize.  But decades later, we’ve learned what it has cost us. Forcing land to produce more than nature intended with chemical fertilizers is like me having to put in 70 hour work weeks on uppers.  Eventually, both the land and I are going to self-destruct, affecting everything in our wake.  Artificially propped up by speed, I may be able to function temporarily on this mad schedule. But besides the adverse effects on body and mind (if you don’t know what I’m talking about, you need a refresher on Breaking Bad), I’d probably be an insufferable maniac to co-workers and family. It’s a vicious cycle.  An organism builds tolerance over time, so after the initial productivity, more chemicals are required.Land stripped of nutrients and toxic with chemicals becomes sick and unable to protect itself;  plants that grow in this environment are stressed and susceptible to diseases like blight.  Pollinators that feed on the toxic plants become sick and die. Declining bee population is largely linked to pesticides and habitat loss and in the US, winter losses commonly reach 30-50%. And drift-prone weed-killers like dicamba kill valuable food sources for bees—weeds.  Bees have been in serious decline over the last decade.  Pollinators, especially honeybees, are responsible for one in every three bites of food we take, according to the USDA.  You get the picture.  All these fertilizers, pesticides and herbicides are killing our pollinators.But they’re also killing us.  200,000 people die every year of acute pesticide poisoning worldwide, according to a UN report released in 2017.  That doesn’t include chronic illnesses and other diseases attributed to indirect exposure such as in contaminated food. And then there’s Roundup.To be continued…Interested to learn more? Read my companion posts on Cooking Subversive:I Cook to Reclaim My Health Superpowers of the Garden Get full access to Cooking Subversive at cookingsubversive.substack.com/subscribe

As the president of the Borlaug Foundation and granddaughter of the “father of modern agriculture”, Julie Borlaug's roots run deep in the fight against global hunger and extreme poverty. Today, in her work with the Foundation, Julie works to combat both through education and boots-on-the-ground international agricultural development. Join us for a CoffeeTalk that discusses the history, the present and the future of agriculture and what our roles as agriculturalists can be to share the story of agriculture. Our third installment of our Women in Ag series! --- Send in a voice message: https://anchor.fm/agisuretrack-coffee-talk/message

First join author Marc Dweck and Associate Editor Victoria Delgado as they discuss the article "Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial." Then, join authors Torbjørn Omland and Geeta Gulati as they discuss the article "Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol." Dr. Carolyn Lam: Welcome to Circulation On The Run. Your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center, VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Hooray, it's another double feature week! And guess what, these two papers are two randomized control trials. One looking at progression of aortic stenosis and the other, looking at a prevention of cardiac dysfunction following adjuvant breast cancer therapies. Dr. Carolyn Lam: So, very interesting two papers coming right up. But Greg, why don't you start by highlighting some of your favorite papers from today's issue. Dr. Greg Hundley: You bet Carolyn. Dr. Greg Hundley: So my first study was conducted by Dr. Gabriela Trifan and colleagues from University of Illinois who performed a meta analysis of major studies that compare the efficacy and safety of dual anti-platelet therapy versus monotherapy for secondary prevention of recurrent stroke or transient ischemic attack in those previously experiencing minor non cardioembolic stroke. And their primary outcomes were stroke and the composite of stroke, TIA, acute coronary syndrome and death of all cause. And the safety outcome was major hemorrhage. Dr. Carolyn Lam: Oh, okay. Very important study. What did they find? Dr. Greg Hundley: Right Carolyn. So the analysis included 27,358 patients. And compared with monotherapy, dual anti-platelet therapy reduced the risk of recurrent stroke and the composite outcome, but increased the risk of major bleeding. And in subgroup analysis at less than or equal to 30 days, dual anti-platelet therapy increased the risk of hemorrhage relative to monotherapy. In sensitivity analyses, the risk for hemorrhage with less than or equal to 30 days of dual anti-platelet therapy, after excluding the combination of aspirin plus Ticagrelor, was comparable to monotherapy. However, the risk of stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remained decreased compared to monotherapy. Dr. Greg Hundley: And so Carolyn, the take-home message from this paper is that dual anti-platelet therapy decreases the risk of recurrent stroke and composite events compared with monotherapy. But, dual anti-platelet therapy increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus Ticagrelor. Dr. Carolyn Lam: Ah, thanks for that last take home message. Thank you. Dr. Carolyn Lam: Well, the paper I'm going to tell you about is the first to examine the role of epicardial fat derived extracellular vesicles in the pathogenesis of atrial fibrillation. And this comes from Dr. Leor from Sheba Medical Center, Tel Aviv University in Israel and his colleagues who collected epicardial fat specimens from patients with and without atrial fibrillation during elective heart surgery. Dr. Carolyn Lam: Epicardial fat samples were grown as organ cultures and the culture medium was collected every two days. And the authors then isolated and purify these epicardial fat extracellular vesicles from the culture medium. Dr. Carolyn Lam: They found that epicardial fat extracellular vesicles of patients with atrial fibrillation had unique pro-inflammatory, profibrotic and proarrhythmic properties. Epicardial fat extracellular vesicles could in fact induce cellular, molecular and electrophysiological remodeling that could result in atrial fibrosis, myopathy and the development of atrial fibrillation. Dr. Greg Hundley: Wow Carolyn, so what are the clinical implications of epicardial fat extracellular vesicles? Dr. Carolyn Lam: Hmm, good question. Well, understanding their role in the pathogenesis of atrial fibrillation may for one lead to the discovery of new diagnostic markers or new targets for the prevention and treatment of atrial fibrillation. And that combined pro-inflammatory profibrotic and proarrhythmic effects of these epicardial fat and extracellular vesicles may in fact be relevant to the pathogenesis of other cardiovascular diseases associated with obesity and abnormal adipose tissue deposition. Dr. Greg Hundley: Very nice Carolyn. Dr. Greg Hundley: My next paper comes again to us from the world of preclinical science and these authors led by Dr. Masanori Aikawa from Harvard Medical School applied a systems approach in mouse experiments to discovering therapeutic targets for vein graft failure. They use global proteomics and high dimensional clustering on multiple vein graft tissues to identify potential pathogenic mechanisms. And experiments were conducted in both in vivo mouse models and in vitro human macrophages. Dr. Carolyn Lam: Oh wow. So what did they find? Dr. Greg Hundley: So Carolyn, peroxisomes proliferator activated receptors or PPAR alpha agonism by pemafibrate retarded the development and inflammation of vein graft lesions in mice, while gene silencing worsened plaque formation. Pemafibrate also suppressed arteriovenous fistula lesion development. Dr. Greg Hundley: Now, metabolomics, lipidomics, functional metabolic assays and single cell analysis of cultured human macrophages revealed that PPAR alpha modulates macrophage glycolosis, citrate metabolism, mitochondrial membrane sphingolipid metabolism and heterogeneity. Dr. Carolyn Lam: Okay. So what is the take home message Greg? Dr. Greg Hundley: Right Carolyn, thought you would ask me that. Dr. Greg Hundley: So PPAR alpha activation suppresses the development of vein graft and arterial venous fistula lesions. And PPAR alpha reduces macrophage activation by influencing macrophage heterogeneity, mitochondrial integrity, and the metabolome. So Carolyn, given that peripheral arterial disease and chronic kidney disease prevalences are increasing, warranting needs for more vein grafts and arterial venous fistulas, this target discovery platform is applicable to investigating therapies for these diseases. Dr. Greg Hundley: And a really nice accompanying editorial is provided by doctors Reilly and Bornfeldt. Dr. Greg Hundley: Well Carolyn, how about we turn to look at what is in the mailbag this week? Dr. Carolyn Lam: Well let me tell you about it Greg. We've got a cardiovascular case series by Dr. Borlaug on things are not always as they seem, multimodality exercise assessment and evaluation of dyspnea. In cardiology news by Kuhn there's a discussion of Evinecumab approval adds a new option for homozygous familial hypercholesterolemia with a hefty price tag. A perspective piece by Dr. Watkins on time to think differently about sarcomere negative hypertrophic cardiomyopathy. And finally a research letter by Dr. Ahn on reduction in Kawasaki disease after non-pharmaceutical interventions in the COVID-19 era, a nationwide observational study in Korea. Dr. Carolyn Lam: Wow. That wraps it up for the summaries. Let's go on to the feature discussions shall we, Greg? Dr. Greg Hundley: You bet. Dr. Carolyn Lam: We are about to talk about the extended follow-up results of the PRADA trial. Oh, so interesting. So happy to have with us today, doctors Geeta Gulati and Dr. Torbjørn Omland, both from the Akershus University hospital in Norway, and you would probably recognize that Dr. Torbjørn Omland is also one of our associate editors, but both here are the co-corresponding authors of this beautiful paper. Dr. Carolyn Lam: Thank you so much for coming here today. Torbjørn, maybe you could start with what is the PRADA trial? Why did you decide to do an extended follow-up? Dr. Torbjørn Omland: Yeah so PRADA was a two times two factorial randomized double blind clinical trial that sought to evaluate the effects of intervention with receptor blocker Candesartan. And a beta blocker Metoprolol in patients with early breast cancer who received anthracycline therapy as part of their chemotherapy. And then we wanted to assess the effect of this sort of preventative therapy, left ventricular function and injury. Dr. Torbjørn Omland: So we reported the primary results of the trial a few years ago and showed that intervention with Candesartan most associated with a significant elevation of the reduction in left ventricular ejection fraction that these patients may experience, and also that treatment with the beta blocker Metoprolol was associated with an intimation of the increase in cardio proponents suggesting a beneficial effect on myocardial injury. However, whether these results were or these effects were sustained after termination of the study drugs was unknown. And that was what we really wanted to address with extended follow-up study. Dr. Carolyn Lam: Yeah, makes a lot of sense, especially because these injuries I suppose could still continue. And just to be very clear, the medications though were only taken during the adjuvant chemotherapy and therefore could be a variable duration from what I understand. Right? Great. Dr. Carolyn Lam: So Geeta then, could you tell us what did the extended analysis show? Dr. Geeta Gulati: The extended follow-up was interesting and it was something we really wanted to figure out because there are not many studies who have been done on the extended follow-up and you're not giving these study medications afterwards. Dr. Geeta Gulati: So very interestingly we saw that the decline in the ejection fraction was still there in the whole group. But this time there was no difference in the group who received Candesartan do those who didn't. And we show that there was a different in the primary results, but now in the extended follow-up there was no difference. And then also in the Metoprolol group that had previously shown that there was lesser rise in the troponins. Again, there was no difference in the groups now on the extended follow-up. Dr. Geeta Gulati: So this is very interesting because this shows that there is a small, modest decline in a left ventricular ejection fraction during and after the breast cancer therapy. But what does this really mean? It's a small decline and it's within the normal range and the cardioprotection is not working. So, are we perhaps looking at the wrong group? Perhaps we should look at patients who have the higher cardiovascular risk factors. Perhaps even we should look at more novel heart failure or cardiac drugs that may have a stronger effect on the ejection fraction. Dr. Carolyn Lam: Right. So Geeta though, can we unpack that a little bit? You see, the patients were not on the medication anymore at the time of follow-up. So you're saying that even though they were given adjuvant chemotherapy and covered with the drug, that even not having any more chemotherapy, their ejection fraction still fell. And if I'm not wrong, this was an MRI analysis. And so it was only by an ejection fraction of two percent on mean fall, right? How do we think about that clinically? Dr. Geeta Gulati: And that's the important question, isn't it? Because a decline in the ejection fraction of less than two percent within the normal range, what does it really mean? Well initially we thought that if there was a different in those who had cardioprotective medication compared to those that didn't, it may prevent development of further decline in the cardiac function and then heart failure in the future. But now, there is really no difference between the groups. So perhaps the clinical implication of giving cardio protection to all cancer patients is not really that useful. Perhaps they should look at those who are at higher risk because they would have a greater fall in ejection fraction and then more cardioprotective effect of these drugs. Dr. Carolyn Lam: Yeah, totally. And perhaps the metrics that we're used to seeing in the past with greater falls of ejection fraction, maybe it just doesn't apply currently or perhaps with the specific chemotherapeutic regimens perhaps that you're using now. Because with a very small fall, and I believe you only had one heart failure event, right? If I'm not wrong in this extended follow-up. So, just to let the audience know, it was very small fall, little number of events. It's hard to really tease apart what that clinically means. Now, could I ask though, does it mean we need actually a more sensitive marker? Because there was some interesting stuff about global longitudinal strain. Could you- Dr. Geeta Gulati: I would throw that question back to Torbjørn I think. Dr. Torbjørn Omland: Yes. So that's a very interesting question Carolyn. So we did observe what seemed to be a beneficial, but a sort of minor effect on global longitudinal strain. So we know that that is the more sensitive index of systolic function than left ventricular ejection fraction, that was the pre defined primary outcome. So that's raises of course questions whether a future trial should more focus on these more sensitive indices of cardiac function. Dr. Carolyn Lam: Yeah. Geeta, could I then really put it back to you? And the tough question I always get, how do we apply these results clinically then? I mean, you see these patients right? Now what? Do you give or do you don't give? And which one do you give? And how do you identify high risk patients? I don't know. Dr. Geeta Gulati: Again, I think all the patients are unique aren't they? So that's where we have to start. So in my clinic, if I have a high risk patient with hypertension, diabetes, hypercholesterolemia, yeah perhaps they even have had a cardiovascular disease before something like this. Then I will take more care of these patients and be more careful with the echo measurements I'm doing and if I find that they have a decline in their cardiac function, I may be more eager to start them on cardioprotective medication. Dr. Geeta Gulati: But then in R-Regen we follow all the HER two positive breast cancers with echo. If I don't have echoparamaties that clearly tells me that they have a decline in the cardiac function, then I may wait to start cardio protection because none of the studies has really so far show that all patients should have these cardioprotective medication or prevention. Dr. Carolyn Lam: Nice. Thank you. That was a tough one to get at. And I suppose Torbjørn I have to give you another tough one then. Because how to address the remaining unanswered questions, right? Because one of them on my mind too, is how to identify the high risk, do biomarkers play a role? And then the other is if we then start the preventive therapies like ERBs and beta blockers, should we actually continue it forever? And so on. But anyway Torbjørn please, please, what does the future hold? Dr. Torbjørn Omland: I think it's worthy of a recap or underscoring that these are really good news for many breast cancer patients that actually the risk of an important decline in ventricular function is lower than we thought. So that may be because of several things. I think in general, those whose used these cardiotoxic drugs are lower. And we also, I think that there's increased collaboration between oncologists and cardiologists. Also meaning that we are better to pick up the high-risk patients at an early stage. Dr. Torbjørn Omland: But of course, it's very important questions that you asked regarding how to identify the high risk patients. And I think that's where really future research should focus. So there we know that traditional risk factors are important. We are looking into whether biomarkers can be used, if there's more sensitive imaging in this can be used. But so far we haven't really succeeded in getting the risk model that really identifies it on the patient level. So that's work that remains to be done. Dr. Torbjørn Omland: And then we are also looking for new types of intervention, good exercise, good other drugs. We are doing now a PRADA two study where we look at the effects of Sacubitril Valsartan in this setting. And those are also very exciting, I think, and we look very much forward to present that in the future. Dr. Carolyn Lam: Oh wow thank you so much Torbjørn and Geeta. The PRADA two trial. I've got to ask you, why do you then call it the Chanel trial? But I think I'll save that for another day. So thank you. Thank you once again, this is fabulous and congratulations to you both. Dr. Torbjørn Omland: Thank you. Dr. Geeta Gulati: Thank you. Dr. Greg Hundley: Well listeners, welcome to our second feature discussion today. And we have with us Dr. Marc Dweck from University of Edinburgh in Scotland and our own associate editor, Victoria Delgado from Leiden in the Netherlands. Welcome to both of you. Dr. Greg Hundley: Marc, we're going to get started with you. Could you tell us a little bit about the background for your study and what was the hypothesis that you wanted to test? Dr. Marc Dweck: Thanks very much Greg for the invitation. So I guess aortic stenosis is perhaps the last major cardiovascular condition where we don't have a medical therapy. We're unable to treat these patients. We're unable to prevent progression. We're only left with a valve replacement. And so we, like a lot of groups around the world, want to develop a treatment for aortic stenosis. Our group did the first SALTIRE trial, where we looked at statins seeing if we could slow aortic stenosis progression. And that, like similar trials, was neutral. No effect on the valve progression. Dr. Marc Dweck: And so actually I've spent the last 10 years looking at some of the factors associated with aortic stenosis progression in particular. The answers that we've had from those trials have kind of come back telling us that really it's a process of calcification. If you look at what triggers progressive valve narrowness is this calcific process, that seems to be a self perpetuating disease. Dr. Marc Dweck: So the question is, how do you target this calcification process? How can you interrupt it? And how can you do that without compromising bone health in these elderly patients? So in trying to come up with a solution to that we thought about using osteopetrosis agents, which we hypothesized would maintain both bone health and reduce vascular calcification on the basis of observational data and also animal data suggesting that. And that was really where we came from in the design of the SALTIRE two trial. Dr. Marc Dweck: And doing a big trial with clinical endpoints wasn't felt to be feasible and instead we decided to look at imaging end points and see whether we could slow disease progression using these agents. Dr. Greg Hundley: Very nice Marc. And so you're really leading us into, tell us a little bit more about your study population and your study design. Dr. Marc Dweck: Yeah so we wanted to take patients from our outpatient clinic with mild, moderate and even early severe disease, asymptomatic patients crucially, patients that aren't scheduled for aortic valve replacement and see the effects of these drugs on disease progression. Dr. Marc Dweck: So we did a randomized control trial. There was three arms. Patients were randomized to Alendronate, Denosumab, these are the two osteopetrosis agents, or placebo. We then did a series of baseline imaging tests. So the primary end point was based on CT calcium scoring. So they had a baseline CT calcium score. They also had a baseline echocardiogram and they had a baseline fluoride PET scan. So this measures calcification activity in the valve. And then we essentially repeated those tests after a period of time on the drugs, or on placebo. We repeated the calcium score and the echo after two years and repeated the PET scan after one year. Dr. Greg Hundley: Very nice, and so before you tell us your results, a little bit, how many patients? And maybe their average age and the rough distribution of men versus women. Dr. Marc Dweck: Yeah so study recruited roughly 50 patients in each arm. The average age was 72 and there was 21% females in the study. So, like a lot of studies in aortic stenosis, a low female prevalence. Despite our best efforts, that's something we need to attend to in the future, but otherwise, a representative age group and patients with this disease. Dr. Greg Hundley: And what did you find? Dr. Marc Dweck: Well we found that the drugs didn't have an effect on any of these imaging assessments. So, there was no effect on the progression for CT calcium score at two years, no effects on any of the echocardiographic assessments of hemodynamic severity, and no effect on calcification activity as measured with the fluoride. Dr. Marc Dweck: So a very consistent result using multiple different imaging modalities, which I think gives us confidence that there isn't at least a dramatic effect of these drugs on disease activity or disease progression, in aortic stenosis. Dr. Greg Hundley: Very good. Well listeners, we're now going to turn to one of our associate editors, Dr. Victoria Delgado, and she is really a valvular heart disease expert member of our team. Dr. Greg Hundley: Victoria, I know you see a lot of papers that kind of come across your desk. What attracted you to this manuscript? And then how do you put the results in the context of other research that's going on to halt the progression of aortic stenosis. Dr. Victoria Delgado: Thank you Greg. So first the first thing that attracted my attention for this article is the question. We know that we don't have any medical therapy for halting the progression of aortic stenosis. And even if the previous studies have been negative or neutral, still there is the interest of trying to find a less invasive therapy for these patients, or even prevent that they arrive to surgical or transcatheter aortic valve replacement. Dr. Victoria Delgado: And the second is that these are very strong analysis because it's a randomized clinical trial and using as end points imaging. So that trial also in a way answers the question of which imaging technique we need to use in order to see the effects of specific therapies. Previous studies have used mainly echocardiography, but that only gave us information on the modynamic effects of the aortic stenosis. While in this study, we have the combination of CT and a combination of a PET that he give us also information on how the calcification is happening. So that makes the study very comprehensive and give us more insights into this pathophysiology, to this pathology particularly. Dr. Greg Hundley: Very nice. So it sounds like looking at aortic stenosis from multiple different angles, whether it be echocardiography or perhaps imaging processes that look at the progression of calcification. Dr. Greg Hundley: Well, Marc, I want to come back to you. What do you think is the next, sounds like you've been working in this area for an extended period of time. What do you see as the next research study that you and your group may undertake in this area? Dr. Marc Dweck: I Think we've got the study design about right. I think if in the future studies we want to do, I think we would adopt a similar design using these imaging end points. Dr. Marc Dweck: I have to say I'm very influenced by the recovery trial that has been conducted in the UK with COVID. I mean, here's a disease where we wanted to get a treatment as quickly as we can. And in doing that, developing a platform type trial where you potentially test multiple different promising agents simultaneously across multiple centers across the world or the UK, I think that would be the quickest way to developing a treatment. And so I'm encouraged that there are five or six very good targets where we could, for a new therapy in aortic stenosis. And I think a platform type design where we engage multiple groups using imaging as that initial end point. And then, the drugs that appear to have an effect on these imaging end points we can start to recruit more patients at those sites, into those centers, looking for clinical end points. Dr. Marc Dweck: I think that kind of discussion is happening around the world now between groups that are interested because we want to crack this problem quickly. We don't want to wait and do these different studies sequentially. We want to try and do them simultaneously. And I'm excited about that. I think if we do that, we've got a real shot at developing a treatment over the next five to 10 years say. Dr. Greg Hundley: Fantastic. Dr. Greg Hundley: And Victoria, I know you have interest in this particular area. Do you have anything you'd like to add? Dr. Victoria Delgado: Yeah. I think that those studies that Mark said are really welcome and I hope that they are positive. And give us a little bit of more to treat these patients. My main fear is that these patients are not as frequent, for example, as heart failure patients. Where we have several therapies where we have possibility to enroll patients in trials for new drugs, that we know that probably are going to be effective. But for valvular heart disease it has been always the end point to reach surgery or to reach an aortic valve replacement or indication of the mitral valve and mitral valve repair. So in early phase of the disease, my main concern is that maybe the patient is not going to be well-trained to understand what are the consequences. I want to always wait until maybe when is needed for the surgical or transcatheter procedure. Dr. Victoria Delgado: But I think that increasing the awareness of the prevalence of valvular heart disease and the consequences may help people to understand, to put more attention for an early diagnosis and develop new drugs that can help, like in this case, aortic stenosis one of the most frequent valvular heart disease, to prevent the proliferation and to prevent the replacement of the valve. Dr. Greg Hundley: Very nice. Well listeners, this has been a wonderful discussion and we greatly appreciate the input that we've been able to gather today from Dr. Marc Dweck from Edinburgh in Scotland and our own associate editor, Dr. Victoria Delgado. Bringing this information from a randomized trial, evaluating osteoporosis drugs, and really indicating they did not disrupt the progression of calcification in patients with aortic stenosis. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, we want to wish you a great rest of your week and we will catch you next week on The Run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.  

The World Food Prize was created by Nobel Peace Prize winner and father of the Green Revolution, Dr. Norman Borlaug to honor those who have made significant and measurable contributions to improving the world's food supply. To date, there have been 50 laureates, with the 2021 World Food Prize winner to be announced in May. Barbara Stinson was named the second president of the World Food Prize Foundation in 2020. In a career spanning over 3 decades, she has focused on improving global food security and safety while addressing the impact of climate change on agricultural productivity. Her work emphasizes policies and programs that support smallholder farmers, especially women and youth, by bringing institutional support and access to new tools, technologies and data to improve the quantity, quality and availability of food. You can learn more about the World Food Prize at www.worldfoodprize.org. Visit their website to read about past laureates, programs and events, or to nominate someone for one of the awards described by Barbara in this episode. To learn more about Dr. Borlaug and the Green Revolution listen to Episode 42 where we discuss the impact of his life and career.

Julie Borlaug is vice president of external affairs for Inari. She is also president of the Norman Borlaug Foundation which continues Dr. Borlaug's work with a mission of fighting global hunger and extreme poverty through international agricultural development. Dr. Borlaug was known as the father of the Green Revolution which was credited with saving a billion lives. He received numerous international awards and recognition for his accomplishments and was one of only 5 individuals including Mother Teresa and Dr. Martin Luther King, Jr. to receive the Nobel Peace Prize, Presidential Medal of Freedom, and Congressional Gold Medals. In this episode, Julie explains what it was like growing up as Norman Borlaug's granddaughter and how he was once upstaged by a hamster. She addresses some of the criticisms of the Green Revolution and how Dr. Borlaug's legacy lives on in modern agriculture. You can interact with Julie on Twitter @julieborlaug.

Dr. Elsa Murano, the former president of Texas A&M and current director of the Borlaug Institute for International Agriculture, joins Innovators to talk about the world's food production system and how it has been disrupted during the pandemic. Dr. Murano was appointed Under Secretary of Agriculture for Food Safety in the United States Department of Agriculture in 2001 and served until 2005, which she went to work at Texas A&M. In 2007, she became the first Hispanic-American and first woman to hold TAMU's presidency. Her current leadership of the Borlaug Institute helps to carry on the legacy of Dr. Norman Borlaug by overseeing the Institute and its international agriculture training programs. Innovators is a podcast production of Harris Search Associates.  *The views and opinions shared by the guests on Innovators do not necessarily reflect the views of the interviewee's institution or organization.*

If you don't know who Norman Borlaug is, you are not alone BUT need to listen to this episode.  Norman has been responsible for saving billions of lives based on his research and revolutionary breeding.  Early on he was responsible for helping Mexico, India and Pakistan become self-sustaining in their wheat production during a time of possible famine!  This is the 50th anniversary of Dr. Borlaug receiving the Nobel Prize for Peace. You will want to share this episode with your friends, family, customer, and colleagues. 

Dr. Norman Borlaug was an American agronomist who specialized in wheat breeding. Known as the Father of the Green Revolution, he helped other hunger fighters save hundreds of thousands of lives in Mexico, India, Pakistan, and other countries throughout his long and varied career. He won the Nobel Peace Prize in 1970 and founded the World Food Prize to celebrate other food fighters worldwide. This episode we speak with his granddaughter and colleague Julie Borlaug and fellow colleagues Dr. Ronnie Coffman and Dr. Ed Runge to discuss the “Man who Fed the World.” Listen to learn: What are the three major improvements Dr. Borlaug contributed to wheat breeding What role sports played in Dr. Borlaug’s life What was the Green Revolution What obstacles still remain in the realm of hunger fighting If you would like to find transcripts for this episode or sign up for our newsletter, please visit our website: http://fieldlabearth.libsyn.com/ Contact us at podcast@sciencesocieties.org or on Twitter @FieldLabEarth if you have comments, questions, or suggestions for show topics, and if you want more content like this don’t forget to subscribe. If you would like to reach out to Julie, you can find her here: julie@inari.com https://twitter.com/JulieBorlaug https://www.linkedin.com/in/julie-borlaug-3b7b6710/ If you would like to reach out to Ronnie, you can find him here: wrc2@cornell.edu If you would like to reach out to Ed, you can find him here: e-runge@tamu.edu Resources CEU Quiz: https://www.certifiedcropadviser.org/education/classroom/classes/873 Leon Hesser’s book, The Man Who Fed the World: https://www.barnesandnoble.com/w/man-who-fed-the-world-leon-hesser/1100451132 Roger Thurow’s book, The Last Hunger Season: https://www.barnesandnoble.com/w/the-last-hunger-season-roger-thurow/1110792507 Roger Thurow’s book, Enough: https://www.barnesandnoble.com/w/enough-roger-thurow/1116903601?ean=9781586488185 Noel Veitmeyer’s book, Our Daily Bread: https://www.amazon.com/Daily-Bread-Essential-Norman-Borlaug/dp/0578095556 Charles C. Mann’s book, The Wizard and The Prophet: https://www.barnesandnoble.com/w/the-wizard-and-the-prophet-charles-c-mann/1126242716?ean=9780345802842 PBS Special, The Man Who Tried to Feed the World: https://www.pbs.org/wgbh/americanexperience/films/man-who-tried-to-feed-the-world/ Norman Borlaug Heritage Foundation: https://www.normanborlaug.org/ Norman Borlaug Institute for International Agriculture: https://borlaug.tamu.edu/ Borlaug Global Rust Initiative: https://www.globalrust.org/ Borlaug Global Rust Initiative Twitter: @globalrust, https://twitter.com/globalrust Borlaug Global Rust Initiative Facebook: @globalrust: https://www.facebook.com/globalrust World Food Prize: https://www.worldfoodprize.org/ The Rockefeller Foundation: https://www.rockefellerfoundation.org/ University of Minnesota: https://twin-cities.umn.edu/ Texas A&M University: https://www.tamu.edu/ Cornell Global Development Department Twitter: @CornellGlobal, https://twitter.com/CornellGlobal Cornell Global Development Department Facebook: @CornellGlobal, https://www.facebook.com/CornellGlobalDevelopment/ Cornell College of Agriculture and Life Sciences: https://cals.cornell.edu/ Cornell College of Agriculture and Life Sciences Twitter: @CornellCALS, https://twitter.com/CornellCALS Cornell College of Agriculture and Life Sciences Facebook: @CornellCALS, https://www.facebook.com/CornellCALS Cornell University: https://www.cornell.edu/ Cornell University Twitter: @Cornell, https://twitter.com/Cornell Cornell University Facebook: @Cornell, https://www.facebook.com/Cornell Iowa State University: https://www.iastate.edu/ CIMMYT: https://www.cimmyt.org/ USDA: https://www.usda.gov/ Alliance for Science: https://allianceforscience.cornell.edu/ Global Youth Institute: https://www.worldfoodprize.org/en/youth_programs/global_youth_institute/ World Food Program: https://www.wfpusa.org/  World Food Programme: https://www.wfp.org/   Peace Corps: https://www.peacecorps.gov/ Bill & Melinda Gates Foundation: https://www.gatesfoundation.org/ Alliance to End Hunger: https://alliancetoendhunger.org/ Sponsored by Gasmet Technologies. Gasmet Technologies range of portable analyzers are used for environmental research measuring CO2, CH4, N2O, NH3 & H2O gas fluxes simultaneously at sub-ppm levels. Check out www.gasmet.com for more information and to request a quotation. Field, Lab, Earth is copyrighted to the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.

Norman Ernest Borlaug (Cresco, 25 de março de 1914 — Dallas, 12 de setembro de 2009) foi um engenheiro agrônomo estadunidense Borlaug formou-se em agronomia pela Universidade de Minnesota em 1942, graduando-se em genética e patologia vegetal. Foi para o México e envolveu-se em pesquisas que resultaram no desenvolvimento de diversas cultivares de trigo de alta resistência e produtividade. Nosso Apoia-se: https://apoia.se/bgscast --- Send in a voice message: https://anchor.fm/bgscast/message Support this podcast: https://anchor.fm/bgscast/support

This week’s episode includes author Charlotte Andersson and Associate Editor Naveed Sattar as they discuss familial clustering of aortic size, aneurysms, and dissections in the community. TRANSCRIPT: Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary, and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke national University of Singapore. Dr Greg Hundley: And I'm Greg Hundley, director of the Pauley Heart Center at VCU health in Richmond, Virginia. Well, Carolyn, our feature this week has to do with aortic size, aneurysms, and predilection to dissection. But before we get to that, how about if we grab a cup of coffee and go through some of the other articles in the issue? Dr Carolyn Lam: I got my coffee, Greg, and you know what? I'm going to start with quiz for you. Dr Greg Hundley: All right. Dr Carolyn Lam:  True or false, in the setting of obesity and/or diabetes, cardiac substrate metabolism shifts towards increased fatty acid oxidation, while lipid accumulates in the heart? True or false? Of course, you're right. Oh, but there's a part two. Can you guess, by increasing fatty acid oxidation, will we induce or prevent obesity-induced lipotoxic cardiomyopathy? Dr Greg Hundley: I'm going to say, because you asked it in the way you asked it, prevent. Dr Carolyn Lam: Wow. All right. Well, the truth is we didn't really know before today's paper. The specific link between cardiac metabolism and lipotoxic cardiomyopathy was elusive and there was no specific therapy available for this condition. And these authors, Dr Rong Tian from University of Washington and colleagues, hypothesized that cardiac pathology-associated obesity would be attributable to the imbalance of fatty acid supply and oxidation. So using a diet-induced obesity model in the current study, they demonstrated that enhancing fatty acid oxidation through deletion of acetyl-CoA carboxylase 2, was sufficient to prevent obesity-induced cardiomyopathy. So, increasing cardiac fatty acid oxidation alone does not cause cardiac dysfunction, but instead protects against cardiomyopathy in chronically obese mice. The cardiac-protective effect of increasing fatty acid oxidation and obese mice is through maintenance of Parkin-mediated mitophagy, and thus preventing mitochondrial dysfunction. These findings indicate that impaired mitophagy contributes to mitochondrial dysfunction in obese mice, and that targeting the Parkin-dependent pathway is a viable therapeutic intervention for obesity-induced cardiomyopathy. Dr Greg Hundley: Very nice. Carolyn. Dr Carolyn Lam: I'm going to be greedy and go on to my next paper. So Greg, do you think cardiac regeneration is possible? Dr Greg Hundley: Well, Carolyn, I would have said, several years ago, no, but that trip that we took to China with Joe Hill and Hesham Sadek, our Associate Editor and our Chief Editor, convinced me otherwise. So I'm going to definitely answer yes on this one. Dr Carolyn Lam: Oh, Greg, you're just too smart. And speaking of China, this next paper is from there, from co-corresponding authors, Dr Nie and Hu, from Fuwai Hospital National Center for Cardiovascular Disease and Chinese Academy of Medical Sciences and Peking Union Medical College. So, using seven genetic mouse lines, they identify that Oncostatin M is the top upregulated cytokine during neonatal heart regeneration. Oncostatin M is a pleiotropic secretory protein that belongs to the interleukin 6 family, and associates with the pathological process of dilated cardiomyopathy. And these authors found that macrophages promote heart regeneration by secreting Oncostatin M, which promotes cardiomyocyte proliferation via a co-receptor, gp130. Employing RNA-seq and functional screening, they further found that Src-mediated gp130 triggered cardiomyocyte proliferation by activating the downstream signaling pathway involving Yap, with Y357 phosphorylation independent of the Hippo pathway. So the last thing that they did was show that gene therapy with adenovirus-associated virus and coding this activated gp130 improved heart regeneration and pumping function, thus serving as a potential therapeutic target. An amazing paper. Dr Greg Hundley: Very nice, Carolyn. What a great summary and so much detail. Well, Carolyn, I'm going to turn our attention to catecholaminergic polymorphic ventricular tachycardia. And this article comes to us from Dr Jason Roberts, from the Western University. Carolyn, genetic variants in calsequestrin 2 can cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia, though isolated reports have identified arrhythmogenic phenotypes among heterozygotes. So in this study, a total of 112 individuals, including 36 catecholaminergic polymorphic ventricular tachycardia probands, 24 were homozygotes for compound heterozygotes, and 12 were pure heterozygotes, against 76 family members possessing at least one presumed pathogenic calsequestrin 2 variant. These were all identified. Dr Carolyn Lam: Wow, a very precious cohort. So what did they find, Greg? Dr Greg Hundley: This international multicenter study of calsequestrin 2 catecholaminergic polymorphic ventricular tachycardia really redefined its heritability and confirmed that pathogenic heterozygous calsequestrin 2 variants may manifest with a catecholaminergic polymorphic ventricular tachycardia phenotype, indicating a need to clinically screen these individuals. Among individuals heterozygous for a pathogenic calsequestrin 2 rare variant, medical therapy and exercise restriction are likely not necessary in the absence of the catecholaminergic polymorphic ventricular tachycardia phenotype. Though, you have to be certain over time, an intermittent clinical screening to ensure they remain phenotype-negative should be obtained. Dr Carolyn Lam: Wow, Greg, clinically important study there. Well, I'm going to go back to the basic science world and talk about calcineurin. Now, calcineurin has long been implicated in the induction of pathological cardiac remodeling but has not been therapeutically targetable for the prevention of heart failure because of its pleiotropy and our lack of understanding of its specific protein-protein interactions and compartmentation within the cardiomyocyte. Dr Greg Hundley: Okay. Carolyn, do you want me to give background on calcineurin? Dr Carolyn Lam: No, Greg, you're off the hook. I'm going to give you some background on calcineurin. So, calcineurin is the calcium-calmodulin-dependent phosphatase that exists as a heterodimer, consisting of a catalytic subunit and a regulatory subunit. Now, of the three catalytic subunit isoforms, alpha, beta, gamma, it's the beta isoform that appears to be the most important for the development of cardiac hypertrophy. Binding of calcium to the calcineurin regulatory subunit enables binding of the calcium-calmodulin complex, thereby releasing auto-inhibition and freeing the enzyme to dephosphorylate downstream substrates. That's the background. Now, in today's issue, we have this great paper from co-corresponding authors, Dr Kapiloff from Stanford University, and Dr Nikolaev from University Medical Center Hamburg. And, with their colleagues, they described the discovery of a calcineurin catalytic subunit beta binding protein Cdc42-interacting proteins 4, and I'm going to call that CIP4, which functions as a scaffold to sequester the pool of calcineurin near the sarcolemma of cardiomyocytes, where it regulates pro-hypertrophic signaling. These findings have really important implications for understanding how cardiac calcineurin is selectively activated by stress signals, as opposed to the pleiotropic second messenger, calcium, that really floods the cardiomyocytes during each contractile cycle. Furthermore, the data provide proof of concept for an innovative therapeutic approach, whereby CIP4-anchoring activity is selectively inhibited to block the action of a small pathogenic pool of calcineurin as a means of treating heart failure. How about that? This is really discussed in an elegant editorial by doctors, Woulfe, Travers, and McKinsey. Dr Greg Hundley: Very interesting, Carolyn. Sounds like another possibility for treating and managing heart failure. Well, let me share with you some of the other findings in our mailbag this week. First, I've got, from Professor Lang Li and Stephen Wiviott, they swap research correspondence regarding the prior publication entitled, Effect of Dapagliflozin on Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus, Insights from the DECLARE-TIMI 58 Trial. And then Professor Laszlo Littmann has a nice ECG challenge for us related to a high-risk ECG that exposed some downstream worrisome vital signs. Dr Carolyn Lam: In addition, there's a perspective piece by Dr Nambi discussing the fact that a zero-calcium score is desirable, but isn't enough to defer therapy, given that up to one-third of events will occur in this group. There's also an In Depth paper by Dr Borlaug, entitled, “Altered Hemodynamics and End Organ Damage in Heart Failure, The Impact on the Lung and Kidney,” and oh boy, this one is so beautifully illustrated. Just a must read for the understanding of the hemodynamics in the lung and kidney and heart failure. Next is a research letter by Dr Loeys on enrichment of rare variants in the Loeys-Dietz syndrome genes in spontaneous coronary artery dissection, and not in severe fibromuscular dysplasia. And finally, another research letter by Dr Arora on racial differences in serial NT-proBNP levels in heart failure management with insights from the GUIDE-IT Trial. What a rich issue, but let's move on to our future discussion, shall we? Dr Greg Hundley: You bet, Carolyn. Well, listeners, we're now getting to our feature discussion and it's very interesting this week where we're going to evaluate aortic aneurysms. And we have with us one of the lead authors of this paper, Dr Charlotte Andersson from Boston Medical Center, and our own Associate Editor, Naveed Sattar from Glasgow, Scotland. Charlotte, welcome to our feature discussion. Could you tell us a little bit about the background and the hypothesis that you put forward with this study? Dr Charlotte Andersson: The background for this study was based on clinical work and what we observed in clinic. We had a few patients where we had been stricken by the fact that they came in with an acute aortic syndrome and they had a first-degree relative themself with the condition, but they did not look syndromic at all. And we started to wonder, what is the actual risk in the community, in people without obvious syndromic features of suffering from an aortic event itself. And although there are quite a few studies out there that have, to some degree, focused on the familial clustering of aortopathies, there is not a lot of information based on communities and whole entire populations. So we wanted to, frankly, estimate what is the incidence rates of aortic dissections and aortic aneurism in the community if you have a first-degree relative that has suffered from the disease themselves. Dr Greg Hundley: How you organize your study and what was your population and what was your design? Dr Charlotte Andersson: This study was actually based on two independent samples. First, we used the Framingham Heart study population that is very densely phenotypes over many years of spanning three generations of participants, where we looked at people who had at least one parent who had an aortic size in the upper quartile index to body-surface area and adjusted for age and sex. And we saw what's the risk of you, as a child, having an aortic size in the same upper quartile. And second, we looked in the general Danish population, the Danish healthcare system is, as you probably know, governmental funded and we have very good registries of all hospitalizations, all outpatient visits, and so we were able to link more hard clinical events in people with and without a first-degree relative. What we did was we started time when people had an aortic dissection, we identified all the first-degree relatives in these people, and we matched them with up to 10 sex and age match controls from the general population without a first-degree relative with the disease. Dr Greg Hundley: What did you find? Dr Charlotte Andersson: We found that in the Framingham sample, if you had at least one parent who belongs into the upper quartile of aortic size, you had an odds ratio of two to three, adjusted for various clinical risk factors, such as hypertension and smoking yourself. And in Danish population, we found that if you had a first-degree relative with an aortopathy, the hazard rates for you developing the disease yourself was almost a tenfold-increase compared to age and sex match controls. And importantly, seemed like hazard ratios use were, more or less, unchanged when we start adjusting various known risk factors, such as bicuspid aortic valve, Marfan syndrome, and Ehlers-Danlos syndrome, normally those kinds of things. And we also found that the younger your proband were at the time of an acute event, the higher was your relative risk yourself. So among people who were below the age of 50 when they suffered an event, the hazard ratios were up to a 50-fold increase. Dr Greg Hundley: Very nice. Naveed, what attracted you to this article as it was coming through the editorial process? And then second, how do we take the information that Charlotte's just conveyed and will be published here today, how do we take this in the context of what we already know about aortic aneurysms? Dr Naveed Sattar: I think it's a beautiful study, so well done, Charlotte. I think it's a beautiful fusion. As Charlotte said, an in-depth cohort study, which has got very well-measured parameters of systematic points and a fantastic population-based data set from Denmark, which Sweden shares and Scotland shares and relatively small countries like us share. So small countries like Denmark punch above their weight in these kinds of studies, which is fantastic. But there's a rich seam of research that comes from these, and this is one of them. So I think that fusion of two data sets with different strengths and limitations combined giving off same signals is good. I think, as Charlotte said, this is the first major population study to look at this question. So there's been people around the world who have got this sense that the aortic aneurism may well be familial, this provides, probably, some of the best data to suggest, yes, it definitely is. Now the questions going forward is, okay, at what point do you screen everybody's got a family history with a proband, or do you screen those who've got a family history of younger probands? And I think what Charlotte and the team and other people around the world thar are going to look at this say, "Okay, we now think, in addition to screening, for example, in the UK and the US we probably screen just men above 65, where most of the disease is, do we also then implement screening in younger people with family histories? And who do we screen, and when and how? And do we need to develop some kind of risk score?" And then when we do that screening, what do we do about it? Is going to be the questions and I'm sure Charlotte and her colleagues have thought about these things and it'd be interesting to see what her view is on those things. But I think it was a beautiful study in every sense. Dr Greg Hundley: So Charlotte, he's really set you up nicely, what study do we need to perform next in this area? What are you and your group thinking about? Dr Charlotte Andersson: Yeah, I think there are two implications of this study. First, clinical, as Naveed says. They already had a sense that aortic diseases were heritable, and I think these data definitely support that we should probably screen first-degree relatives. And I think, at some extent, this is what the guidelines already encourage us to do. So I'm not sure it would be feasible to randomize people or do a clinical trial where we screen some but not others. I'm not sure that would be ethical. I think the evidence is too strong for familial clustering and that we should probably screen these people. But I think also, our estimates, they are so strong that I suspect that there are likely more genetic variants associated with non-syndromic aortopathies that we are not aware of just yet. So I think the next step would be to try to disentangle the genetics a little bit more. I have seen some preliminary analysis based on the UK Biobank, for instance, and I think there are more genetic variants to come up with also, more common genetic variants, at least, that we are not aware of just yet. So that would be the next step as I see it. Dr Naveed Sattar: And that might particularity in younger probands. Dr Charlotte Andersson: Right. Dr Naveed Sattar: Those with the younger probands, because it looks like, as you said, the hazard ratio, the risks, are so high, it could also potentially be monogenic, but anyway. Dr Charlotte Andersson: I agree. Dr Greg Hundley: Well, Charlotte, Naveed, we really appreciate your time and taking this opportunity to discuss these really interesting findings and helping us understand that, truly, there may be a familial component to understanding this disease process, particularly in patients with aortic aneurysms that may go on to develop aortic dissections. Well listeners, we hope you have a great week and on behalf of Carolyn and myself, catch you on The Run next week. This program is copyright, the American Heart Association, 2020.  

O Sobretudo está de regresso com um episódio importante e urgente, apesar de não ter a atenção que merece, nos ciclos noticiosos e na discussão pública. Falei com Sara Baga sobre sementes e sobre a nossa relação como património vegetal do planeta, com um foco especial na acção humana, no passado, presente e futuro. Tinha especial interesse em saber mais sobre o que se está a passar com as patentes de sementes e sequências genéticas de produtos naturais (biopirataria, como viria a aprender nesta conversa). A Sara é activista e formadora, e tem estado a desenvolver uma série documental sobre este tema, que ela apresenta também um pouco no final da conversa. Outros recursos importantes para complementar a conversa, ou que tenham sido mencionados no episódio: Eleven reasons why Europe needs to ban patents on food plants and farm animals Food & agriculture | Corporate Europe Observatory Seed Freedom Transgénicos Fora No patents on seeds Syngenta's healthy tomatoes (sobre a patente do tomate) https://pubmed.ncbi.nlm.nih.gov/1932678/ (Sobre a manipulação de morangos com genes de peixe) O Guardian sobre Borlaug e a revolução do trigo que "salvou milhões de pessoas"  O World Nutrition Journal sobre a patente da Nestlé sobre leite humano (Se os links não estiverem visíveis ou acessíveis na app de podcasts, podem ser visitados em podcastsobretudo.pt/sementes)   ::::::   Subscreve o Sobretudo e segue-nos no twitter, facebook e instagram como @sobretudocast.Ouve o Sobretudo no Spotify e na tua aplicação de podcasts ou mesmo no site, onde podes encontrar todos os episódios: podcastsobretudo.pt Agora também já podes apoiar o Sobretudo de diferentes maneiras. Muito obrigado ao Diogo Constantino pelo apoio como mecenas do Sobretudo.Visita o Clube Amigos do Sobretudo para te tornares também mecenas e ajudar o Sobretudo a crescer. O Sobretudo é um projecto de Márcio Barcelos e o genérico é dos Cayena.

The virtual meeting of the National Association of Plant Breeders took place last week. In our final podcast from the proceedings we talk with Borlaug Scholar Tia Dunbar about her rice research. Dunbar is obtaining her MS degree in Plant Breeding at Texas A&M University in College Station, TX. Originally hailing from the San Francisco […] The post Nanotechnology and the Future of Rice: Borlaug Scholar Tia Dunbar appeared first on Seed World.

Which person can be credited with having saved the most human lives in history? There might not be a direct answer to that question, but one person whose name always comes up is that of Normal Borlaug.  Borlaug has been called “Humanity’s Forgotten Benefactor” and was the winner of the Nobel Peace Prize. His efforts have been attributed to having saved the lives of over a billion people. Yet, few people know who he is.Learn the inspiring story of the man who saved the world on this Episode of Everything Everywhere Daily. -------------------------------- Get your free one month trial of Audible.com http://www.audibletrial.com/EverythingEverywhere -------------------------------- Executive Producer James Makkyla Become a supporter on Patreon: https://www.patreon.com/everythingeverywhere Instagram: https://www.instagram.com/everythingeverywhere/ Twitter: https://twitter.com/everywheretrip Reddit: https://www.reddit.com/r/EEDailyPodcast/ Website: https://everything-everywhere.com/everything-everywhere-daily-podcast/

As Day 3 of the National Association of Plant Breeders annual meeting gets underway, we chat with four Borlaug Scholars all working in many different crops, but with a focus on wheat. The post Enter the World of Wheat with 4 NAPB Borlaug Scholars appeared first on Seed World.

As Day 3 of the National Association of Plant Breeders annual meeting winds down, we talk with Borlaug Scholars William Singer and Clayton Carley about the world of soybeans. The post Talking Soybeans with Borlaug Scholars William Singer and Clayton Carley appeared first on Seed World.

The 2020 meeting of the National Association of Plant Breeders continues! Borlaug Scholar Natalie Kaiser is a Ph.D candidate in the Potato Breeding and Genetics Program at Michigan State University. She is employing molecular and genomic tools to understand the genetic architecture of host plant insect resistance and to develop Colorado potato beetle (CPB) resistant […] The post Propagating Potato Via True Seed: NAPB Borlaug Scholar Natalie Kaiser appeared first on Seed World.

The 2020 virtual meeting of the National Association of Plant Breeders began today. We sit down with Borlaug Scholar David Tork to talk about the intricacies of modern flax breeding. Tork is a second-year MS student at the University of Minnesota-Twin Cities. After gaining initial plant breeding experience as an intern at Dow AgroSciences (now […] The post Just the Flax: NAPB Borlaug Scholar David Tork appeared first on Seed World.

The 2020 virtual annual meeting of the National Association of Plant Breeders (NAPB) begins today! In our ongoing series of podcasts being released this week, we talk to Borlaug Scholar Chandler Levinson — the only one of this year’s scholars whose speciality is peanuts. Levinson is a Ph.D student studying plant breeding, genetics, and genomics under […] The post Peanuts and Cave Exploration: NAPB Borlaug Scholar Chandler Levinson appeared first on Seed World.

Announcement of the 2020 Winner   ~ Juan Tricarico, Ph.D., VP Sustainability Research, Dairy Management Inc. and CAST President Sponsor Comments   ~ Julie Borlaug, Board of Directors, CropLife Foundation Concluding Remarks   ~ Kent Schescke, Executive Vice President, CAST

When famine ravaged India in 1966, the nation turned to one man: a small-town Iowan obsessed with wheat. Rob Rapley joins host Krys Boyd to talk about Norman E. Borlaug, who won praise for his work on disease resistance crops – which also came with unintended consequences. His American Experience film “The Man Who Tried to Feed The World” airs tonight on PBS stations.

Agronomist Norman Borlaug led a "Green Revolution" of agriculture programs estimated to have saved one billion lives. A history professor joins us to talk about Borlaug's complicated legacy.

Agronomist Norman Borlaug led a "Green Revolution" of agriculture programs estimated to have saved one billion lives. A history professor joins us to talk about Borlaug's complicated legacy.

Heroes of Progress is an outstanding Series created by HumanProgress.org by author Alexander C Hammond.Check out the rest of the Heroes of Progress by subscribing or going to the playlist: https://www.youtube.com/playlist?list=PLyxK8N8FZsA02jnZKolX6Et7MBduqg8n4You can find the source content here: https://humanprogress.org/article.php?p=1498https://humanprogress.org/sub?cid=100&sid=270Truth + Character + Wisdom = Prosperity.*******************************************************************WHERE YOU CAN LISTEN TO/READ MY CONTENT:► TruthSeeker Newsletter- http://bit.ly/ohytruthseeker► PODCAST: SPREAKER- https://www.spreaker.com/show/oh-hale-yeah► PODCAST: iTunes - http://bit.ly/ohysubscribe► PODCAST: Google - http://bit.ly/OHYGoogle► QUORA - https://goo.gl/31USZa► MEDIUM - https://goo.gl/fMTWZR► TWITTER- https://goo.gl/85RFf2► PAYPAL- www.paypal.me/OHHALEYEAH► SUBSCRIBE - https://www.youtube.com/c/OhHaleYEAH********************************************************************All footage taken falls under ''fair use'' of the Digital Millennium Copyright Act (1998). Therefore, no breach of privacy or copyright has been committed. Freedom of speech is the ability to speak without censorship.***************

Ken chats with Jon Boeckenstedt, vice provost for enrollment at Oregon State University, and the mind behind Higher Ed Data Stories, a treasure trove of data-driven (and data-visualized) observations about the state of higher ed. Jon shares some views about his recent career move as well as surprises about his reading and writing habits, as well as the unusual upside of the imposter syndrome.Shout-outs & LinksA couple of other places to get your Boeckenfix: jonboeckenstedt.net and Out Here In Oregon.The Test and The Art of Thinking a documentary about standardized tests, their role in college admission, and how they do (and don't) predict academic success. Jon's early influences that inform his wonderment about the absurdity of life: Mad Magazine's Snappy Answers to Stupid Questions (Vol. 1-3); The Stranger by Albert Camus; and Monty Python.500px and Flickr, two collections of Jon's photographyAn investigative report on whether Alex Bello is, in fact, Marlon Jackson's Episode sponsored by InitialView and their latest development, Elevator Pitch.Rapid DescentWalkout song: Won't Get Fooled Again by The Who.Best recent read: A Wikipedia entry about Norman Borlaug, which inspired him to name March 25 (Borlaug's birthday) National Test-Optional Day.Eager to read next: The Years that Matter Most by Paul Tough ("Apparently I'm in it...")Favorite thing to make in the kitchen: Semi-homemade killer chili: Hormel chili + extra sharp cheddar + Frank's Red Hot + bacon bits.What he uses to take and keep notes: Not much of a notetaker, but Jon loves a good fountain pen. Though he owns a Montblanc, he prefers his Sheaffer (for writing in black) and Lamy (for writing in blue).Memorable bit of advice: "Everybody is an imposter." Bucket list: "I do not and never have had a bucket list."

Vi snakker om Hans Rosling, positive nyheter og tre personer som har gjort det mulig å brødfø en voksende verdensbefolkning. Innslag av Magnus Lomax Bjerke. Lenker: https://humanprogress.org/ How not to be ignorant about the world | Hans and Ola Rosling https://www.youtube.com/watch?v=Sm5xF-UYgdg

In 1970 the American scientist, Norman Borlaug, was awarded the Nobel Peace Prize for his pioneering work developing disease-resistant crops. At the time famine and malnutrition were claiming millions of lives across the world, particularly in South Asia. Dr Borlaug’s work meant countries like India were able to become self-sufficient. Critics said the new grain varieties were too reliant on chemical fertilizers, but it’s thought millions of lives were saved. Rebecca Kesby has been speaking to Professor Ronnie Coffman, student and friend of Norman Borlaug. (Photo: Dr Norman Borlaug in a field of wheat. Credit CIMMYT International Maize and Wheat Improvement Centre)

In the second hour, hosts Fr. Richard Kunst and Fr. Ryan Moravitz joined David Borlaug to talk about the upcoming Bismarck-Mandan Symphony Orchestra performance for January. Our hosts then took listeners on our 10-Minute Tour of local events. The Diocese of Duluth's Deacon John Foucault spoke about a popular program in Duluth called Theology Uncapped and plans for helping it to continue to grow. Finally, Fr. Rich and Fr. Ryan spoke with Susan Safford of the Diocese of Rapid City about an opportunity to refuel our spiritual lives with the source and summit of our Catholic faith.

In the second hour, hosts Fr. Richard Kunst and Fr. Ryan Moravitz joined David Borlaug to talk about the upcoming Bismarck-Mandan Symphony Orchestra performance for January. Our hosts then took listeners on our 10-Minute Tour of local events. The Diocese of Duluth's Deacon John Foucault spoke about a popular program in Duluth called Theology Uncapped and plans for helping it to continue to grow. Finally, Fr. Rich and Fr. Ryan spoke with Susan Safford of the Diocese of Rapid City about an opportunity to refuel our spiritual lives with the source and summit of our Catholic faith.

Dr Amit Khera:                  Welcome to Circulation on the Run, your weekly summary and backstage pass to the journal. I'm Dr Amit Khera, associate editor and digital strategies editor from UT Southwestern Medical Center in Dallas. And I have the privilege of standing in for Dr Carolyn Lam, your usual weekly podcast host. Today we have a special treat. It is our semiannual fellows and training FIT podcast. And the additional part of this treat is we have three very special FITs today. These are our assistant editors for social media for Circulation. And really I want to introduce you just a moment, but I want to thank these three for their hard work and efforts. It really is them that helped bring our social media to life. And importantly for us, we really have a commitment to enhancing fellow education involving fellows in our editorial process and really making sure that the journal is appealing to fellows in training. So we really rely on these three to help us understand what best resonates and what is most helpful for fellows in training. So without further ado, Jainy Savla from UT Southwestern. Welcome Jainy. Jainy Savla:                         Thanks for having me on the podcast today. Dr Amit Khera:                  And we have Daniel Ambinder from Johns Hopkins University. Hi Dan. Daniel Ambinder:             Hey Amit. Thanks for having me on the podcast today. Dr Amit Khera:                  Absolutely. And finally we have Jeff Hsu from UCLA. Hi Jeff. Jeff Hsu:                               Hi Amit and hi everyone. Very glad to be here. Dr Amit Khera:                  Well, Jainy, I'm going to start with you. You've been with us on the social media side the longest. I think it's maybe almost a year or a bit more that you've been working on these efforts. And again, very much appreciate all of your hard work and insight. Tell us a bit about yourself. Jainy Savla:                         So I'm currently a research fellow at UT Southwestern. So I completed my general cardiology training and I've been doing some extra research training in one of our basic science labs there. Dr Amit Khera:                  So not surprisingly with your background, do you select an article? So we've asked them each to select one article as they've been working through the social media side and see all of our articles come through. Each to select one that they found was interesting and perhaps summarize for us what it included and what appealed to them. So Jainy, tell us a little bit about the article you chose and why you chose it. Jainy Savla:                         So, I chose one of the articles that was published in April of 2018 from the Molkentin team lab. And this is a basic science article that focused on which types of cells contribute to heart regeneration. They hadn't thought that there was cardiac progenitor cell that could contribute to the development of new cardiomyocytes. And more recent data has shown that maybe that's not quite the case. So what this study did was used a lot of fancy lineage tracing models to try to figure out which types of cells we're actually contributing to the development of new cardiomyocytes. So importantly, what came from this was that one of their models, they were able to delete two transcription factors that are necessary for cardiomyocytes to develop from these progenitor cells. But they found that when they did that, they even got a higher number of cardiomyocytes that formed. And then what they were able to show in this paper was that actually comes from fusion of leukocytes to cardiomyocytes. And then interestingly, they found a role for one of these transcription factors and the development of endothelial cells. So that was kind of a new, not known function of one of these genes that was previously thought to be just contributory to cardiac development. Dr Amit Khera:                  It's really a fascinating article when you think about it. Most of the science we publish are people bringing to light new discoveries and certainly there was a component of that here. But in many ways, it was kind of a different article where there had been this a prevailing thought about these c kit positive cells and here they're actually had gone through, refuted what people had thought was happening with these in this de novo cardiomyocyte formation. So you'll see that very often where people's articles or work is headed out to sort of maybe refute or set right what's happening in the literature in the field. Can you comment on that as to that type of article and how that appealed to you in this study? Jainy Savla:                         That is interesting because previously it has meant that these cells can be used as a therapeutic option in human patients. But some of them were recent data showed that perhaps the new cardiomyocytes weren't actually coming from these cells, but it was hard to say. So the nice part about this paper was really they used a lot of important lineage tracing models to really show where these cells are coming from. And it helped clarify some of the, I guess, more confusing science that had been in the field since there were a few papers that showed these cells were contributary and then a few papers that have shown that maybe they weren't. So I think that's really helpful, particularly when you're talking about things that could be potentially used as therapeutic agents in human. And also the interesting thing is that while these cells themselves may not be useful to perhaps harvest and give to someone, you could potentially alter these cells and then they produce cells that fuse with cardiomyocytes. Or could you use this a different way? So I thought that was also interesting about this article. Dr Amit Khera:                  Great points in it. It does remind us again that in our enthusiasm for rushing things to clinical practices in some things in this field, the importance of rigorous basic science to really understand the molecular underpinnings. And as you mentioned, there's some new insights here that could be used for clinical therapeutic purposes in the future. So definitely an interesting article and glad you enjoyed it and brought it to our attention. I'm going to ask you a bit of a different question. You again have been working with this in the social media side for longer. You've seen this now for some time about the different articles that come through. I know you and I've had several conversations about our different platforms, Twitter or Facebook, and how they're different and how we engage with them and how we engage with the audience. Can you tell us a little bit just reflecting now on your time and working with social media from a journal perspective, kind of what you've learned? What are some interesting observations over this year? Jainy Savla:                         Definitely one interesting observation is just that their general usage of these social media platforms has increased significantly since I've started doing this. And you can see this with when we get articles that are accepted, how many authors have Twitter handles that they'd like to be tagged in some of these posts. And that's just gone up significantly since I've started doing this. And that also changes sort of what the comments we get on some of the posts and the back and forth discussions that we're seeing on these platforms. And then the second thing I found really interesting over time is that the way people use Facebook is really different from the way people use Twitter. And you can follow the discussions that people have linked to our posts a little bit better on Facebook. And then on Twitter, there's also a lot of similar discussions about these posts. But they kind of manifest in different ways and it's really interesting to see how that plays out. Dr Amit Khera:                  I think those are fantastic points. And from a fellow's perspective, how do you think fellows are engaging with social media now compared to maybe, I don't know, when you started your training a few years back. What have you seen in a positive light? Jainy Savla:                         I mean in general, there are more fellows on Twitter now than when I was a first-year fellow. Even myself, I've got my Twitter account when I was in fellowship. I didn't have one prior to that. I mean it's interesting because people are able to showcase their work a little bit better I think with these types of handles whereas before maybe you wouldn't know that even one of your own co fellows had published something. So it's kind of nice to see people use that kind of as a networking tool in some ways or to showcase some of their own work, which is something that when I was a first year and I didn't have a Twitter handle and there weren't as many fellows on Twitter, I didn't really notice some of the work that's being done by some of my colleagues at my level. Dr Amit Khera:                  Those are great points and I'll stoplight some of the things you just said talking about it being a way for fellows to really showcase their work, to help with networking and in some ways, it's sort of the great equalizer. So I think it's really a valuable platform specifically for fellows. Well thank you Jainy. I'm going to move on to Daniel and hear a little bit from Daniel. Tell us a bit about yourself. Daniel Ambinder:             I'm currently a second year cardiology fellow at John's Hopkins Hospital and I plan on doing interventional and structural cardiology in the future. Dr Amit Khera:                  Great and certainly a lively and growing field and so many exciting things happening. Well, it's interesting you chose an article today that is more of a clinical article and obviously quite different than the last one we heard, but equally as interesting. Tell us a little about the article you've chose and why you chose it. Daniel Ambinder:             I was very excited about this article that was published in Circulation back in July 2018. So, it's by Dr Borlaug and Reddy on how to diagnose HFpEF and what they did was they took patients with clinical dyspnea and they used invasive human dynamics to kind of assess whether or not they had HFpEF. And by doing so they were able to generate a list of clinical and eco based guidance to help us kind of identify patients with heart failure with preserved ejection fraction. So they came up with this amazing little table which was featured in Circulation and on Circulation twitter, where they have a chart that basically goes through several clinical variables including weight and hypertensiveness, atrial fibrillation, pulmonary hypertension, being elderly. And filling pressure is based on echo cardiographic information. And by that they were able to generate a score and give you a probability of if your patient has HFpEF or not.                                                 And the reason why I really enjoyed reading this article and also posting this article was because going through internal medicine and not being so fundamentally aware of echo and kind of what goes into understanding left ventricular filling pressures, it was challenging to make a diagnosis of heart failure with preserved ejection fraction. Do you just basically say, "My patient has lower extremity swelling but normal EF? They have heart failure with preserved ejection fraction and [inaudible 00:09:32] on the [inaudible 00:09:33]. And so I thought that this would be really helpful to the medical community at large. And in fact, shortly after we posted it, I saw that our cardiology console fellow is actually utilizing this exact table to help one of the medicine teams manage a patient with lower extremity swelling and come to the diagnosis of heart failure with preserved ejection fraction. So that is why I chose this article for today. Dr Amit Khera:                  That's a great article and I thought you summarized it very well. And it is a field. HFpEF you'd see a lot of articles in Circulation on this topic. We have many people that are interested from an editor’s level but also from a society level. This is a huge problem, but we know very, very little. And I'm sure you know that as well and this was a wonderful tool. Just shows you're sort of the beauty and simplicity. Although if you read it, the message were pretty rigorous and they had a lot of great work that they did to develop it. But I love that the H2 HFpEF, how they basically came up with it h for heavy and the f from fibrillation. So I thought that was incredibly creative and a very simplistic but useful score. So, you said your, tell us about yourself. Have you used the H2 of the HFpEF score yet? Daniel Ambinder:             Absolutely. I use it in clinic on a daily basis. And I actually pull up the Tweet in my office and show the patients why I think that they have heart failure preserved ejection fraction, especially since many of my patients start to get really nervous when you start talking about heart failure. But then they don't understand that they have a normal functioning heart. They can't really put those two together. And so going through this chart and going through the etiology, or at least what we know about heart failure with preserved ejection fraction, turns out to be quite helpful. Dr Amit Khera:                  And the basis of this study goes back to hemodynamics. This obviously is a cohort where they had done invasive hemodynamics to essentially diagnosed HFpEF based on pressure. So as you, as someone who's going interventional and structural where we are really seeing kind of the rebirth or refocus on hemodynamics again, tell me a little bit like what you're learning in terms of hemodynamics and how you think that importance in today's practice of cardiovascular medicine. Daniel Ambinder:             One of my passions is spending as much time as I possibly can in the cardiac ICU. And we're fortunate to meet many different patients that come in with very different kinds of cardiogenic shock for other hemodynamic compromise from other types of shock. And I have found it extremely helpful to think about either using a virtual Swan or by actually getting the measurements with a PA catheter to kind of identify where the break in the system is to hopefully provide our patients with the ability to turn them around in a fast manner before they develop metabolic compromise from prolonged hypoperfusion. Dr Amit Khera:                  Great summary of how you're using hemodynamics and the training. And I'm going to pivot. The last question for you is when we first met I think several months back and we're communicating about your interest in social media, one thing that was really interesting and fascinating was the great work you're doing on Twitter on your own account where you essentially, if I think you told me this right, you sit on your iPhone and basically in this matter of a very few minutes would construct cases and teaching points on Twitter. So tell me a little bit about that, about using Twitter for medical education and learning cardiology and cases. And I know you're passionate about that. So tell us a little bit more about that. Daniel Ambinder:             Back in May, last year, I had been in my first year of cardiology fellowship. And I was really kind of obsessed with grabbing as much imaging and cases as I could to construct them into teaching stories to share these important stories that I encounter with other people. And so also share the aha moments that I have when I'm learning from my mentors about a new clinical condition or even a clinical condition that I've encountered many times. We never thought about any unique way. And so I was putting these all together and developing somewhat of a library of cases. But I would share them with the residents that I was working with at the time. And then Dr Erin Michos was one of my mentors at Hopkins. She's an echocardiographer and she kind of exposed me to the Twitter community where you're really able to just start reaching out to different people and share the same insights that I had saved on my drive on my computer. And so I started constructing these cases, putting that together and developing them and then associating them with like a few bullet pointed tidbits of pearls that I can put on Twitter. And I quickly realized what an amazing community Twitter have to offer in terms of cardiology and in terms of the medical education community at large.                                                 At first, I realized you can't put out content and not expect to participate in a conversation. It has to be two ways. You have to really engage with others and others will engage with you. And then just a couple months later, it's really grown that you can post a case, post the teaching pearl and in about 24 hours it can be viewed thousands and thousands of times, really internationally. And generates just so much great conversation. So it's been really a tremendous way to communicate with the world, especially within the cardiovascular world. Dr Amit Khera:                  Well thanks. I think there's so much learning that can happen and I think the work you're doing with cases and with others. And I know when I've gone on Twitter, even in just two minutes you can see really fascinating things and learn a lot. So keep up the good work and appreciate your efforts there. I'm going to switch gears and finally finished with Jeff Hsu from UCLA. Jeff, tell us a bit about yourself. Jeff Hsu:                               I'm a fellow at UCLA. So I actually finished my general cardiology fellowship pretty recently and now I'm a research fellow in the STAR program here. I'm also enrolled in the PhD program at UCLA in the Department of Physiology and planning to defend in the next few months. So right now, very stressed out about that. Starting in July, I'll be starting advanced fellowship in advanced heart failure and transplant here at UCLA.                                                 Well excellent and best of luck to you in your PhD defense. Now you also chose a very interesting article that again, all of yours are a bit different. So tell us a little about the article you chose and why you chose it.                                                 When I chose this article, I was really excited by a few weeks ago. It was published in the December 4th issue of Circulation called Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human Induced Pluripotent Stem Cells. So this came out of the lab of Joe Wu at Stanford and the co first authors is Ning Ma, Joe Zhang and Ilanit Itzhaki. But I think the beauty of this article is that it really addressed this frustrating clinical scenario in question that we often encounter nowadays in this era of genome sequencing. And now that we're sequencing a lot more people, since the cost of sequencing has come down a lot, we were finding a lot of these mutations that we don't know what to do with, so I think Dr Wu's lab really try to address this question using the disease model with the cardiomyopathy. So, leveraging Dr Wu's expertise in using human induced pluripotent stem cells or iPSCs, they found a patient who is actually healthy but apparently had this mutation in this gene called MYL3 or myosin light chain 3. And so this patient had a variance of uncertain significance in this gene.                                                 Now, notably, this patient, again had no clinical phenotype, was very healthy and the patient's family members over three generations were all healthy too. But had this mutation that based on in silico analyses was thought to be likely pathogenic. So using cells from this patient that they reprogrammed into cardiomyocyte, they tested various properties of these cells from the same patient to see whether or not they thought this mutation is actually a pathogenic mutation. So again, using these reprogrammed cardiomyocytes, they tested a variety of things including gene expression, sarcomere structure, and cell contractility, action potentials, and the handling of calcium. And they saw that even with this mutation, there were no abnormal findings in vitro in their system.                                                 Now just to prove that their cell culture system and this in vitro model of testing the pathogenicity of certain mutations actually works, they actually took cells from a patient who did have the clinical phenotype as a result of a known mutation that causes hypertrophic cardiomyopathy. And found that when testing those cells in vitro, they did demonstrate abnormal phenotypes in all the parameters I mentioned before. So I thought this is really exciting. I thought this is a great way to address, potentially answer whether or not we think these variants of uncertain significance that we often encounter are indeed pathogenic because we are often just left in this situation where we don't know what to do with this information. But this potentially at least is a proof of concept for this protocol where we can finally take advantage of the ability to take cells from our patient and actually test them in the lab to see whether or not either various treatments work or whether or not these mutations that actually will results in pathology down the line. So I thought overall this was a great paper that was a great summary of how we can take the bedside to the bench actually. And I'm just really looking forward to the future where we can maybe then bring it back to the bedside. Dr Amit Khera:                  Well thanks. I think that's an excellent choice and a great summary. And this article really hit all of the kind of timely and cutting-edge topics in the era genomic medicine and precision medicine have really kind of individualized treatments. And when we get stuck, these VUSes, these are a nightmare. And also this is sort of proof of concept for extending this to other treatments and other ways to test drugs and therapies. I've heard Joe, we talk about this before and use the word disease in the dishes. He did I think in the article itself and it's exactly that. I mean the potential here is profound. I'll pivot this into the next question for you. For our roles, one thing we do is we interact a lot with media and I interact a lot with them to help translate, I guess, the articles that we have to things that would be able to be digestible for media and for lay individuals. It was interesting because it's hard for us to do that with basic science and most of the time we have some difficulty in translating that. But this one translated pretty well and I think we had done some various press releases and things because it really showed the potential of modern medicine and kind of the excitement of it.                                                 But that gets to the question I have for you, something we have discussed as well, your interest in basic science and some of the challenges of taking basic science articles and digesting them down to a couple hundred-word tweet. Even as beautiful as all the pictures are, and in this article I think there's six figures, but each panel is 10 pictures or 10 figures by themselves. And how do we digest basic science articles down to make them really appeal to people on social media and help people understand that may not be in the fields or in basic science that are clinicians, if you will. I know you've thought about that a little bit. Tell me a little bit about your thoughts on that. Jeff Hsu:                               Jainy, Dan and I have this challenge on a weekly basis, figuring out how to summarize great articles such as this one into a short tweet. And I think that is a big challenge particularly for basic science articles on social media to make it appeal to a broader audience because the audience you're seeing on Twitter and Facebook, again, they're not just basic scientists. If you want to catch people's attention, you need to find a way to really understand the big picture of the question you're answering in your basic science research. So I think that is a challenge. You're challenged to make your science appealing to a broader audience. But I think again, that's one of the advantages of social media is that you can appeal to a larger audience and have a wide range of people engage with your research and understand your research. So it is something that we work on is to try to pick out the figure that best represents the science that was done in these basic science articles.                                                 It can be quite challenging because a lot of times one picture won't do it justice. So it's tough to distill a full article in one picture. It is helpful when some articles do have a summary, a graphic or figure where they typically reserve their last figure for either a cartoon or some type of schematic that really explains either the mechanism or pathway that they explored in their article. So what we've found is that these articles that do have some of these illustrations or summary figures, they seem to engage a larger audience on Twitter and social media. So personally I find it more appealing when I do see these summary figures. So if there is one recommendation, I would have the basic science researchers, especially trainees is in this age of social media, try to come up with an illustration or summary figure for your research. I think it helps you figure out what is truly important with the research that you've done and helps you communicate this research to a broader audience. And I've seen a lot of people take advantage of a graphic designers to really help them illustrate their research. And I found that to be very effective in articles I've read on social media. Dr Amit Khera:                  Thanks Jeff. That's a great point and great suggestion. And certainly these days the most effective communicators are those they can translate their complex science into easily digestible bites and can think of ways to portray them in ways that sort of summarize, like you said, be it summary figures or otherwise. And it's a challenge and also talent. And you all are certainly perfecting that. Well, I think we've had an excellent conversation. I have to tell you, I'm so excited to get the chance to spotlight you all. You do excellent work each day. Every week you're working hard and coming up with great ideas and suggestions and we really value having your input as fellows and training and as a colleague.                                                 Thank you for joining us today on our FIT podcast. Amit Khera standing in for Carolyn Lam. We look forward to seeing you for our next edition of Circulation on the Run. This program is copyright American Heart Association 2018.  

Are you a Wizard or a Prophet? Two largely forgotten 20th century thinkers – Norman Borlaug and William Vogt – continue to shape our competing visions of the future of our planet.   In this episode, we talk to Charles C. Mann, award-winning author of The Wizard and the Prophet, about these remarkable scientists and their lasting influence.   Borlaug – the Wizard – is a Nobel-winning scientist who kickstarted the agricultural ‘Green Revolution’, while Vogt – the Prophet – laid the foundations for the modern environmental movement.   The path we choose to solve our environmental dilemmas hinges on how we understand and frame the problems we face. Is innovation and technology the solution that will push us beyond our predicaments to overcome earth’s natural boundaries, or is the answer to scale back and respect the ecological limits of our planet?   Charles and I discuss: Who the Prophets and Wizards are, what they believe in and what they’ve achieved, and how they envision the future Who the contemporary Prophets and Wizards are that continue to shape public debate How these competing visions dictate debates in agriculture, water scarcity, energy, and climate change The politics and power dynamics behind the visions of Prophets and Wizards What’s at stake if we choose one path over another A sobering (and rather terrifying) alternative third vision   Links: Chalres C. Mann ‘Can Planet Earth Feed 10 Billion People?’ The Atlantic Charles C. Mann ‘The Wizard and the Prophet’ William Vogt ‘The Road to Survival’ Noel Vietmeyer 'Our Daily Bread; The Essential Norman Borlaug'   You May Also like: FFS 013 – How Plants Domesticated Humans FFS 011 - Transforming Agriculture to Feed the Future FFS 009 – Stop Generalising GMOs  

This week we're talking Windows 10, Norman Borlaug, and competition. Show music by Reed Love and OGRE. Support the show!

When Norm entered college to major in forestry, he never dreamed God would use that training to help him feed over 1 billion people. Here's Norm's amazing story.

Norman Borlaug and Robert Noyce aren't household names. But these two Iowans influenced the 20th century more than anyone else on Planet Earth. Borlaug created drought and disease-resistant varieties of wheat that thrived in poor soils throughout the planet. Because of him, billions in the developing world avoided starvation (they probably only missed it by about a decade). Noyce invented the integrated circuit and founded Intel. He is the father of Silicon Valley, the digital revolution, and the Internet economy that connects the world.Both men owe their success to their farm roots in Iowa.

Guds plan | Hana Marie Borlaug | 25.feb 2018 by Porsgrunn Misjonskirke

In this interview, Peter A. McCullough and Barry Borlaug discuss the nuts and bolts of pulmonary hypertension in left heart disease.

This week we talk about the story of Norman Borlaug and his fight against famine. We also note some of the theological implications of Borlaug's work. Borlaug was a Nobel Prize winner who died in 2009. His work in the field of agriculture may very well have saved hundreds of millions of lives from famine. He and his teams accomplished this by developing new breeds of wheat and new agricultural methods in Mexico, Pakistan, India, and other countries, at a time when each of these countries faced the prospect of mass starvation. And they did so in the face of powerful political opposition. The Borlaug story shows the value of developing the knowledge, skill, and technique necessary to convert the basic material of the universe, the matter and energy governed by the laws of nature, into the products and services that are important for human well-being. From a theological perspective, we could say that God provides what we need to survive and even flourish, but it is up to us to figure out how to make use of God’s provision and to go to work doing so. The theological point is made in Biblical passages such as Psalm 104:14-15. This process calls for the work of scientists, engineers, technologists, and inventors. But let's not stop there. A broad range of occupations contributes to the process, including the people who design logistics and transportation systems, new ways of organizing information, new forms of organization, new ways of communicating, and all the other activities it takes to sustain this work. These all contribute. And it's not only the big innovations, like those of Borlaug, that really matter. The big innovations cannot usually survive without a whole host of smaller innovations, many of which are almost unnoticeable. And the big innovations themselves are often based on a great many smaller innovations. Of course not everything we produce is beneficial. Wisdom is required, the wisdom to know what should and should not be created. Each of us can probably point to a time when human inventiveness took us in the wrong direction. We need wisdom, more wisdom than we sometimes exhibit. And, you might say, the wisdom that is found in the Bible.

Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. What is the association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy? We will be discussing new data in this area in just a moment, following these summaries.                                                 The first paper describes the effect of long-term metformin and lifestyle measures on coronary artery calcium. This is a paper from Dr. Goldberg of George Washington University Biostatistics Center and colleagues of the Diabetes Prevention Program Research Group. The Diabetes Prevention Program and its outcome study is a long-term intervention study in subjects with prediabetes, which showed reduced diabetes risk with lifestyle and metformin compared to placebo.                                                 In the current study, the authors looked at subclinical atherosclerosis, which was assessed in 2,029 participants using coronary artery calcium measurements after 14 years of average follow-up. They found that men but not women with prediabetes treated with metformin for an average duration of 14 years had lower coronary calcium scores than their placebo counterparts. No difference in coronary calcium scores was observed in the group receiving a lifestyle intervention as compared to the placebo group.                                                 These findings provide the first evidence that metformin may protect against coronary atherosclerosis in men with prediabetes, although demonstration that metformin reduces cardiovascular disease events in these subjects is still needed before firm therapeutic implications of these findings can be made. The reason for an absence of an effect in women is unclear and deserves further study.                                                 The next study provides insights on the physiology of angina from invasive catheter laboratory measurements during exercise. Dr. Asrress of Royal North Shore Hospital in Sydney, Australia, and colleagues, studied 40 patients with exertional angina and coronary artery disease who underwent cardiac catheterization via radial axis and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual GTN was administered to half the patients and all patients continued to exercise for two minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity, and central aortic pressure were recorded using sensor wires.                                                 Using this novel invasive approach, the authors showed that administration of GTN ameliorated angina by reducing myocardial oxygen demand as well as increasing supply with a key component being the reversal of exercise-induced coronary lesion vasoconstriction. This was evidenced by the fact that there was a relationship between the diastolic velocity pressure gradient with significant increase in relative stenosis severity. In keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilation of normal segments, with trends towards reversal with GTN.                                                 Thus, this study describes the development of a paradigm where patients with coronary artery disease can exercise while simultaneously having coronary and central aortic hemodynamics measured invasively, and has shown that this provides a unique opportunity to study mechanisms underlying the physiology of angina. In treating patients with exercise-induced angina, the results highlight the importance of after-load reduction and the use of agents that reduce arterial wave reflection and promote coronary artery vasodilation.                                                 The next study provides mechanistic insights into reverse cholesterol transport, where excess cholesterol is removed from macrophage-derived foam cells in atherosclerotic plaques. It suggests that melanocortin receptor-1, or MC1-R, may play a role. As background, the melanocortin system, consisting of melanocyte-stimulating hormones and their receptors, regulate a variety of physiological functions, ranging from skin pigmentation to centrally-mediated energy balance control. At the cellular level, the biological actions are mediated by G protein-coupled melanocortin receptors, such as MC1-R. MC1-R not only affects melanogenesis in the skin but also has immunomodulatory effects through its wide expression in the cells of the immune system.                                                 In the current study from Dr. Rinne of University of Turku in Finland, and colleagues, human and mouse atherosclerotic samples and primary mouse macrophages were used to study the regulatory functions of MC1-R. The impact of pharmacological MC1-R activation on atherosclerosis was further assessed in apolipoprotein E deficient mice. Their findings identified a novel role for MC1-R in macrophage cholesterol transport. Activation of MC1-R conferred protection against macrophage foam cell formation through a dual mechanism. It prevented cholesterol uptake while it concomitantly promoted reverse cholesterol transport by increasing the expression of ATP-binding cassette transporters, ABCA1 and ABCG1.                                                 Thus, the identification of MC1-R in lesional macrophages, demonstration of its role in regulating reverse cholesterol transport, combined with its established anti-inflammatory effects, suggests that MC1-R could be a novel new therapeutic target for preventing atherosclerosis.                                                 The next study suggests that obesity-related heart failure with preserved ejection fraction, or HFpEF, is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments. First author, Dr. Obokata, corresponding author, Dr. Borlaug, and colleagues from Mayo Clinic Rochester and Minnesota studied 99 patients with obese HFpEF with a BMI above 35, with 96 non-obese HFpEF with a BMI less than 30, and 71 non-obese controls without heart failure. All subjects underwent detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing.                                                 The authors found that, compared to non-obese HFpEF, obese HFpEF patients displayed greater volume overload, more biventricular remodeling, greater right ventricular dysfunction, worse exercise capacity, more impaired pulmonary vasodilation, and more profound hemodynamic arrangements, despite a lower NT-proBNP level. Obese HFpEF patients displayed other important contributors to high left ventricular filling pressures, including greater dependence on plasma volume expansion, increased pericardial restraint, and enhanced ventricular interaction, which was exaggerated as pulmonary pressure load increased.                                                 These data provide compelling evidence that patients with the obese HFpEF phenotype have real heart failure and display several pathophysiological mechanisms that differ from non-obese patients with HFpEF. These and other issues are discussed in an accompanying editorial by Dr. Dalane Kitzman and myself. We hope you enjoy it.                                                 The final study identifies a novel long noncoding RNA that regulates angiogenesis. As background, although we know that the mammalian genome is pervasively transcribed, a large proportion of the transcripts do not encode a protein, and are thus regarded as noncoding RNAs. Based on their length, they can be divided into small or long noncoding RNAs, long being described as more than 200 nucleotides. Although their function is not fully understood, long noncoding RNAs have been increasingly reported to mediate the expression of other genes, affect the organization of the nucleus, and modify other RNAs.                                                 In the current study by first author, Dr. Leisegang, corresponding author, Dr. Brandes, and colleagues of Goethe University in Frankfurt, Germany, epigenetically controlled long noncoding RNAs in human umbilical vein endothelial cells were searched by axon array analysis following knockdown of the histone demethylase JARID1B. The authors discovered a novel noncoding RNA named MANTIS to be strongly upregulated. MANTIS is located in the antisense strand of an intronic region of the gene for annexin A4, calcium- and phospholipid-binding protein. MANTIS is a nuclear long noncoding RNA that is enriched in endothelial cells but also expressed in other cell types. Reducing MANTIS levels led to impaired endothelial sprouting, tube formation, attenuated endothelial migration, and inhibition of the alignment of endothelial cells in response to shear stress.                                                 Brahma-like gene 1, or BRG-1, was identified as a direct interaction partner of MANTIS, implying a role of MANTIS in the formation of the switch/sucrose non-fermentable chromatin remodeling complex. MANTIS binding to BRG-1 was shown to stabilize the BRG-1 interaction, hence by inducing an open chromatin conformation, MANTIS was proposed to maintain the endothelial angiogenic potential. The implications of these findings are discussed in an accompanying editorial by Dr. Zampetaki and Mayr from Kings College London.                                                 That brings us to the end of our summaries. Now for our feature discussion.                                                 Today, we are going to be discussing the association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy. To discuss this, I have the first and corresponding author of our feature paper, Dr. Heather Boyd, from Statens Serum Institut in Copenhagen, and our familiar Dr. Sharon Reimold, content editor for special populations from UT Southwestern. Welcome, Heather and Sharon. Dr. Heather Boyd:            Thank you. Dr. Sharon Reimold:        Thank you. Dr. Carolyn Lam:               Heather, it's a topic that I can't say I'm very familiar with, association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy. Could you start by sharing why would we think there would be a link? What was the hypothesis you were testing? Dr. Heather Boyd:            A couple years ago, there was a paper published in the European Heart Journal that reported evidence of angiogenic imbalance in women with fetuses with major congenital heart defects, so women who were pregnant with babies that had heart defects, and then in fetuses that were terminated because of this kind of defect. My research group focuses a lot of attention on preeclampsia. In the last decade or so, angiogenic imbalance in preeclampsia has been a really hot topic. Women with preeclampsia, particularly women with early-onset preeclampsia, have big angiogenic imbalances. When we saw the European Heart Journal paper, we immediately thought, "What's the connection between preeclampsia and heart defects in the offspring?" Dr. Carolyn Lam:               Oh! Dr. Heather Boyd:            Exactly. That was our entry point to it, was the term "angiogenic imbalance" in that paper sort of was a flag for us. It wasn't a completely new idea, but we in Denmark have one big advantage when considering research questions that involve either rare exposures and/or rare outcomes, and that's our National Health Registry. We have the ability to assemble these huge cohorts and study conditions like heart defects with good power, so we decided just to go for it. Dr. Carolyn Lam:               That makes a lot of sense now. Please, tell us what you did and what you found. Dr. Heather Boyd:            The first thing we did was look at the association between carrying a baby with a heart defect and then whether the mom had preeclampsia later in the same pregnancy. We had information on almost 2 million pregnancies for this part of the study. We found that women carrying a baby with a heart defect were seven times as likely as women with structurally normal babies to develop early preterm preeclampsia. We defined that as preeclampsia where the baby has to be delivered before 34 weeks, so the really severe form of preeclampsia. Then, women carrying a baby with a heart defect were almost three times as likely to develop late preterm preeclampsia as well. That's where they managed to carry it until 34 weeks but it has to be delivered some time before 37 weeks.                                                 These findings were similar to those of other studies, but we were able to go a step further and look at individual heart defect subtypes. What we found there waws that these strong associations were similar across defect categories. Then we decided to see if we could shed any light on the origin of the problem, whether it was coming from the mom's side or the baby's side. To do this, we looked at women with at least two pregnancies in our study period to see whether preeclampsia in one pregnancy had any bearing on the chance of having a baby with a heart defect in another pregnancy or vice versa.                                                 This part of the study included 700,000 women. We found very similar findings. We found that women with early preterm preeclampsia in one pregnancy had eight times the risk of having a baby with a heart defect in a subsequent pregnancy. Late-term preeclampsia in one pregnancy was associated with almost three times the risk of offspring heart defects in later pregnancies. Then, we found that it worked the other way around too. Women who had a baby with a heart defect were twice as likely to have preterm preeclampsia in subsequent pregnancies.                                                 Those results were really, really exciting, because whatever mechanisms underlie the associations between preterm preeclampsia in moms and heart defects in the babies, they operate across pregnancies. Therefore, that pointed towards something maternal in origin. Dr. Carolyn Lam:               That is so fascinating. Sharon, please, share some of the thoughts, your own as well as those of the editors when we saw this paper. Dr. Sharon Reimold:        I think that there's a growing data about the links between hypertensive disorders of pregnancy and preeclampsia with subsequent abnormal maternal outcome. But this paper, I think, has implications for how we look at moms who are going to have offspring with congenital heart defects as well as those with preeclampsia. For instance, I would look at a patient now that has preeclampsia, especially in more than one pregnancy, to identify that they may be at risk to have offspring with congenital defects in the future if they have additional children. But the mom is also at risk based on other data for developing other cardiovascular risk factors and disease as she gets older. It was really the link going back and forth with the hypertensive disorders and the congenital defects that we found the most interesting. Dr. Carolyn Lam:               That struck me too, especially when you can look at multiple pregnancies and outcomes. That's amazing. You know what, Heather, could you share a little bit about what it's like working with these huge Danish databases? I think there must be a lot more than meets the eye. Dr. Heather Boyd:            It's an interesting question, because I'm a Canadian and I was trained in the US. I did my PhD in epidemiology at Emery, and then I moved to Copenhagen. When I first got here, I was absolutely floored at the possibility of doing studies with millions of women in them. It opens some amazing possibilities, like I said earlier, for certain outcomes and certain exposures. You just need to have a question where the information you want is registered. Dr. Carolyn Lam:               Yeah. But I think what I also want to put across is, having worked with big databases, and certainly not as big as that one, it's actually a lot of work. People might think, "Oh, it's just all sitting there." But, for example, how long did it take you to come to these observations and conclusions? Dr. Heather Boyd:            I have a fabulous statistician. I think she's the second author there, Saima Basit. She spends a lot of her time pulling together data from different registers. But yes, you're right. The data don't always just mesh nicely. The statisticians we have working with us are real pros at this sort of data slinging. Dr. Carolyn Lam:               Could I just pose one last question to both of you. What do you think are the remaining gaps? Dr. Sharon Reimold:        I think that this is a clinical link. Then, going back to figure more about what's going on biologically to set up this difference? Because right now there's really no intervention that's going to make a difference, it's just a risk going forward. This is sort of like medicine done backwards, that there's this association and now we need to figure out exactly why. Dr. Heather Boyd:            I can piggyback on what Sharon said a little bit, because I think one of the things we need to remember is that not all women with preeclampsia have babies with heart defects. Not by a long shot. What we need to do now is to figure out what distinguishes the women who do get this double whammy from the vast majority who don't.                                                 One of the things that Denmark does really nicely is that there are large bio banks. One of the things we want to do is go back to bank first trimester maternal blood samples and see if we can identify biomarkers that are unique to the women with both preterm preeclampsia and babies with heart defects. That's one of the things we're thinking about to address this gap. Because, as Sharon says, we've got to figure out what the mechanism is.                                                 The other thing we want to do is to see whether the association between preeclampsia and heart defects extends, for example, to other things, to cardiac functional deficits, for example, because it's probably not just severe structural defects. If there's an association, it's probably on a continuum. Are babies born to preeclamptic moms, do their cardiac outputs differ? Do their electrical parameters differ? Do they just have different hearts?                                                 We're really lucky because right now the Copenhagen Baby Heart Study is offering to scan the hearts of all infants born at one of the three major university hospitals in the Copenhagen area. We're about to have echocardiography data on 30,000 newborn hearts to help us look at this. I'm really excited about that possibility. Dr. Carolyn Lam:               I've learnt so much from this conversation. I'm sure the listeners will agree with me. Thank you both very, very much.

The eggplant (brinjal, aubergine) is a curious fruit in western nations, but is an important staple for hundreds of millions of people worldwide. Today’s podcast discusses the eggplant with Dr. Mark Chapman from University of [...]

Ian and Jesse discuss the current state of genetic modification of agricultural products, and where the technology might lead in the future. If we could add, subtract, and combine any traits we want in our crops, what wondrous things could we create?   Links to topics discussed: FlavrSavr tomato Golden Rice Aquadvantage salmon Norman Borlaug NYT article on GMO products CRISPR Gene guns Civil War urban legend Craig Venter Enviropig C3 vs C4 photosynthesis   Theme music, used with permission, by Jonathan Coulton.

Today’s show is something of a departure; I’m talking about someone who is crucial to global food security and yet who is almost unknown. It’s true, as Jean-Henri Fabre, the French naturalist wrote, that “History ... knows the names of the king's bastards but cannot tell us the origin of wheat.” Most people are blissfully unaware of the men and women who created the plant varieties that keep us fed. I say as much at the beginning of the show, when I guess that perhaps one in a hundred people can name a plant breeder, and that the name they’re most likely to come up with is that of Norman Borlaug. (The true stats, from a very small, self-selected sample, are somewhat different. Two out of 13 – about 15% – can name a plant breeder, although neither of the names they came up with was Borlaug’s.) I thought Borlaug might be the most familiar plant breeder because he is credited as being the Father of the Green Revolution, for work that won a Nobel Peace Prize in 1970. Nazareno Strampelli, an Italian plant breeder, exactly foreshadowed Borlaug’s work by about four decades. His wheats doubled production in Italy and beyond and were crucial to the second green revolution ushered in by Borlaug. He was born on 29 May 1866, 150 years ago as I write this. He deserves to be better known (as do all plant breeders, actually). Notes There is very little about Strampelli’s life and work in English. I am indebted to Sergio Salvi for his books, articles and time, without which I could not have produced this episode. Music for the show graciously provided by Jon Fuller, aside from bits of soundtrack lifted from archive Italian newsreel. The banner image I grabbed from Ridley Scott’s Gladiator; it’s a little in joke for anyone who does know even a smidgen of the history of wheat. There is so much more to the story of Strampelli and the early days of plant breeding; would you be interested in an e-book?

The planet Earth holds over seven billion humans. Somehow, against all manner of predictions to the contrary, we feed all of them. This would have astounded Thomas Malthus who, in 1798, predicted that humanity was careening toward a demographic catastrophe, […]

"The first essential component of social justice is adequate food for all mankind," said Norman Borlaug during his acceptance speech for the Nobel Peace Prize in 1970. In 1977, he was awarded the U.S. Presidential Medal of Freedom and in 2006, the U.S. Congressional Gold Medal, just a few in a long line of honors bestowed upon Borlaug, known as the father of the Green Revolution. In this week's Open Mic, his granddaughter, Julie Borlaug, tells about the promise she made to him on his deathbed about continuing his focus on science and technology to feed a growing, hungry world. As Associate Director for External Relations for the Borlaug Institute at Texas A & M, she talks about several projects to help farmers in developing nations and why those who buy products labeled fair trade may be hurting, rather than helping small farmers.Julie Borlaug

Andy and AT bring special guest Julie Borlaug, granddaughter of Norman Borlaug (whom The Butterfly Effect and The Boy Who Changed the World is about), on the podcast to discuss the legacy of her grandfather’s life-changing work.   Norman Borlaug hybridized corn and wheat for arid climates, which ultimately saved the lives of over 2 billion people across the world from famine. ·      Andy reverse engineered Norman Borlaug’s life in multiple books to show that everything we do matters. ·      He absolutely changed the world. ·      Julie now works for the Borlaug Institute at Texas A&M, which continues the work Norman Borlaug started.   Andy came up with The Butterfly Effect story when the military contacted him about the problem of suicide among soldiers. ·      How do you prove to people that their life matters? ·      He was researching George Washington Carver when he discovered Norman Borlaug.   Julie had the opportunity to work directly with Norman during the last six years of his life. ·      Norman was adamant that we must believe in the young and inspire them and give them the resources to show them they can change the world. ·      He made his breakthrough with wheat in his 30s after everyone told him what he was doing was not going to work. He was even fired and he quit a few times. ·      He was working on a technique called shuttle breeding, and his stubbornness eventually paid off. ·      Norman truly believed that it will be the young who will come up with the solutions to our greatest problems.   If you’re doing what everyone else is doing, you’re probably doing something wrong. ·      Most people aren’t getting extraordinary results. So if you’re doing what everyone else is doing, you’re only contributing to the average. ·      If you want extraordinary results for your life, your marriage, your children, your profession, you have to stop doing what everyone else is doing. ·      Norman Borlaug’s least favorite word was “mediocrity.”   Were you encouraged or helped by this podcast? Share it with a friend!   Questions for Listeners   ·      What would you like to hear Andy discuss on future episodes? o   Phone: 1-800-726-ANDY o   E-Mail: InTheLoop@AndyAndrews.com o   Facebook.com/AndyAndrews Twitter.com/AndyAndrews

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Un informe de la Universidad de Virginia analiza el divorcio cuarenta a

Dr. Norman Borlaug remembers how the Mexican Agricultural Program developed the first high-yield, dwarf varieties of wheat that went on to help produce the Green Revolution. In this video podcast, he reviews how the program started with the help of Henry Wallace, the technical challenges the plant breeders faced, the public relations and political problems of introducing the new varieties, and the results. Mexico became self-sufficient in wheat production in only 12 years, and the Mexican wheat varieties were exported all over the world.

In the 1960s, population scientists predicted that millions would die of starvation in India and Pakistan. That was before Dr. Norman Borlaug and other agricultural scientists introduced dwarf hybrid wheat varieties and modern farming practices into the subcontinent. In this video podcast, Borlaug talks about overcoming technical, psychological, economic and political obstacles to save the lives of millions.

Norman Borlaug says serendipity led him from a background growing up on a farm in Iowa to the winner of the Nobel Peace Prize for his work with the Green Revolution. In this video podcast, Dr. Borlaug says his first life ambition was to be the second baseman for the Chicago Cubs. His second was to be a science teacher with a degree from Iowa State. But a wrestling scholarship led him to the University of Minnesota. He earned a degree in forestry, but then met Dr. E. C. Stakman who convinced him to study cereal grains. That led to his development of high-yielding wheat varieties that saved the lives of millions.