Podcasts about isomorphic

北京时间 5 月 8 日，谷歌 DeepMind 和谷歌旗下子公司 Isomorphic Labs 联合发布了其生物学预测模型 AlphaFold 的最新版本——AlphaFold 3。这是在 AlphaFold 2 发布三年后，谷歌在 AI 生物学领域的又一次突破。和前代相比，AlphaFold 3 的预测效率有了显著提升，而且在蛋白质本身以外，它还能够预测「几乎所有分子类型」的蛋白质复合物结构，有望大幅提升新药研发的效率。 那么具体来看，AlphaFold 3 有什么样的区别和改进？由技术关照现实，这项技术在工业界，尤其是药物设计领域将会带来怎样的应用前景？又会带来哪些变革？本期节目邀请到来自业内和学界的嘉宾，硅谷投资人张璐和清华大学生命学院博士后徐魁，分别从商业与技术的视角深度探讨 AlphaFold 3，聊聊我们应当如何看待 AI 在生命科学领域的应用，以及这项技术目前的优缺点和未来趋势。 「声动活泼」公众号上也同步整理了本期节目的要点，如果你喜爱本期节目或对节目内容感到好奇，欢迎在微信搜索「声动活泼」查看最新文章。 感谢图拉斯对本期节目的支持~ 图拉斯是创立于 2012 年的创新、高品质的 3C 数码品牌，凭借完善的自主研发体系，严苛的品质把控和独特的设计理念，成为行业领导者，多款产品荣获国际设计大奖。如今已经发展成为横跨四大洲、服务 148 个国家和地区的全球化品牌，拥有超过 6000 万用户。 Untitled https://files.fireside.fm/file/fireside-uploads/images/4/4931937e-0184-4c61-a658-6b03c254754d/pVPU50lv.jpeg 图拉斯 yoga 伸缩线充电器，点击链接下单： https://sourl.cn/J6Rtkp （京东） 、https://sourl.cn/aWh4t4 （天猫） - 双口快充——双口共 40WPD 多设备同时快充 - 集成无级调节伸缩线—— 0.68m 随停随收 - 内嵌式折叠脚——安心收纳不刮包 - 专利转轴——高精度压铸锌合金转轴，持久耐用 本期人物 丁教 Diane，「声动活泼」联合创始人、「科技早知道」主播 张璐，硅谷 Fusion Fund 创始合伙人，达沃斯全球青年领袖，斯坦福客座讲师 徐魁，清华大学生命学院博士后，研究方向为计算生物学、人工智能生物学 雅娴，「科技早知道」监制 主要话题 [03:00] 相比 AlphaFold 2，AlphaFold 3 有何区别与改进？ [05:25] Isomorphic lab：专注商业化的帮手 [09:30] 竞争对手在做什么？同领域中美竞争格局 [14:29] AlphaFold 3 无法大幅缩短药物研发周期 [17:53] AlphaFold 3 模型优化：流水线整合为一体化 [22:24] 医药领域 AI 应用：短期被高估，长期被低估 [29:58] 技术的商业潜力：改变世界也创造财富 [32:28] 从药厂 AI 应用说起，开源是行业发展必然吗？ [39:39] 冲突、幻觉、手性错误？AlphaFold 3 仍有局限性 [42:08] 指数级增长的未来与跨学科合作趋势 所涉部分术语 David Baker：美国华盛顿大学医学院蛋白质设计研究所主任。他的实验室专注于蛋白质结构预测与蛋白质设计的工具开发。节目中提到的多个与 AlphaFold2/3 竞争的生物分子预测软件均由 David Baker 实验室主导开发，如 RoseTTAFold、RoseTTAFold All-atom 和 RoseTTAFold2NA。 Autodock Vina ：它是一个开源的分子对接（docking) 引擎，被广泛用于预测小分子（配体）与蛋白质（受体）之间的结合模式。由美国 The Scripps Research Institute 的 Molecular Graphics Lab 开发。 MSA：多序列比对（Multisequence Alignment，简称 MSA）是一种生物信息学技术，用于将三个或以上的氨基酸序列进行比对，以找出它们之间的相似性和差异性。在结构预测中，MSA 能够辅助寻找相似序列蛋白并且比对他们的结构特征，提高预测精度。 Clash：蛋白质模型中，Clash 通常指的是蛋白质内部或蛋白质之间的原子间距离过近，超出了范德华半径所允许的范围，导致的空间冲突或重叠现象。结构预测软件需要尽量减少 Clash 的发生。 AIDD：即人工智能辅助药物发现 （Artificial Intelligence for Drug Discovery）。 ESG：在生物制造领域，ESG 代表环境（Environmental）、社会（Social）和公司治理（Governance）三个方面，是衡量企业在可持续发展方面表现的重要指标, 代表了企业在环境责任、社会责任和公司治理方面的表现。 相关阅读 Accurate structure prediction of biomolecular interactions with AlphaFold 3 (https://www.nature.com/articles/s41586-024-07487-w) #54 AI 进军生物界，AlphaFold 的突破 “将改变一切” (https://www.xiaoyuzhoufm.com/episode/5fd9e96bdee9c1e16d8cd03e?s=eyJ1IjogIjYzOTk0OTJmZWRjZTY3MTA0YTdiMmVkYyJ9) S6E37｜如果 AI 就能解锁蛋白质，世界还需要结构生物学家吗？ (https://www.xiaoyuzhoufm.com/episode/636b8a6d5aca413bf96d1372?s=eyJ1IjogIjYzOTk0OTJmZWRjZTY3MTA0YTdiMmVkYyJ9) 幕后制作 监制：丁教、雅娴、Xinlu 后期：Jack、迪卡 商业内容策划：Nene 运营：George 设计：饭团 商务合作 声动活泼商务合作咨询 (https://sourl.cn/6vdmQT) 支持我们，加入新一年的播客创新 2021 年我们发起了「声动胡同会员计划」，这是一个纯支持项目，支持「声动活泼」在播客内容上不断探索和创新。回顾 2023 年，得益于这些支持，「声动活泼」的每档节目都不断突破，不仅荣登苹果中国的年度热门节目榜单，还在 CPA 和喜马拉雅等平台都榜上有名。2024 年全新付费节目「不止金钱 (https://www.xiaoyuzhoufm.com/podcast/65a625966d045a7f5e0b5640)」现已上线，欢迎收听。同时，新一季「跳进兔子洞」即将上线，敬请期待！ 胡同 https://files.fireside.fm/file/fireside-uploads/images/4/4931937e-0184-4c61-a658-6b03c254754d/Z0YbNKpo.png ​ 加入我们 声动活泼正在招聘全职「节目监制」、「节目营销」、「商业化项目管理」，查看详细讯息请 点击链接 (https://sourl.cn/j8tk2g)。如果你已准备好简历，欢迎发送至 hr@shengfm.cn， 标题请用：姓名+岗位名称。 关于声动活泼 「用声音碰撞世界」，声动活泼致力于为人们提供源源不断的思考养料。 我们还有这些播客：声动早咖啡 (https://www.xiaoyuzhoufm.com/podcast/60de7c003dd577b40d5a40f3)、声东击西 (https://etw.fm/episodes)、吃喝玩乐了不起 (https://www.xiaoyuzhoufm.com/podcast/644b94c494d78eb3f7ae8640)、反潮流俱乐部 (https://www.xiaoyuzhoufm.com/podcast/5e284c37418a84a0462634a4)、泡腾 VC (https://www.xiaoyuzhoufm.com/podcast/5f445cdb9504bbdb77f092e9)、商业WHY酱 (https://www.xiaoyuzhoufm.com/podcast/61315abc73105e8f15080b8a)、跳进兔子洞 (https://therabbithole.fireside.fm/) 欢迎在即刻 (https://okjk.co/Qd43ia)、微博等社交媒体上与我们互动，搜索 声动活泼 即可找到我们。 期待你给我们写邮件，邮箱地址是：ting@sheng.fm 声小音 https://files.fireside.fm/file/fireside-uploads/images/4/4931937e-0184-4c61-a658-6b03c254754d/gK0pledC.png ​ 欢迎扫码添加声小音，在节目之外和我们保持联系。 Special Guests: 张璐, 徐魁, and 雅娴.

In this episode of Gradient Dissent, Isomorphic Labs Chief AI Officer Max Jaderberg, and Chief Technology Officer Sergei Yakneen join our host Lukas Biewald to discuss the advancements in biotech and drug discovery being unlocked with machine learning.With backgrounds in advanced AI research at DeepMind, Max and Sergei offer their unique insights into the challenges and successes of applying AI in a complex field like biotechnology. They share their journey at Isomorphic Labs, a company dedicated to revolutionizing drug discovery with AI. In this episode, they discuss the transformative impact of deep learning on the drug development process and Isomorphic Labs' strategy to innovate from molecular design to clinical trials.You'll come away with valuable insights into the challenges of applying AI in biotech, the role of AI in streamlining the drug discovery pipeline, and peer into the future of AI-driven solutions in healthcare.Connect with Sergei Yakneen & Max Jaderberg:https://www.linkedin.com/in/maxjaderberg/ https://www.linkedin.com/in/yakneensergei/ https://twitter.com/SergeiIakhnin https://twitter.com/maxjaderberg Follow Weights & Biases:https://twitter.com/weights_biases https://www.linkedin.com/company/wandb

Professor Doudna was awarded the 2020 Nobel Prize in Chemistry with Professor Emmanuelle Charpentier for their pioneering work in CRISPR genome editing. The first genome editing therapy (Casgevy) was just FDA approved, only a decade after the CRISPR-Cas9 editing system discovery. But It's just the beginning of a much bigger impact story for medicine and life science.Ground Truths podcasts are now on Apple and Spotify. And if you prefer videos, they are posted on YouTubeTranscript with links to audio and relevant external linksEric Topol (00:06):This is Eric Topol with Ground Truths, and I'm really excited today to have with me Professor Jennifer Doudna, who heads up the Innovative Genomics Institute (IGI) at UC Berkeley, along with other academic appointments, and as everybody knows, was the Nobel laureate for her extraordinary discovery efforts with CRISPR genome editing. So welcome, Jennifer.Jennifer Doudna (00:31):Hello, Eric. Great to be here.Eric Topol (00:34):Well, you know we hadn't met before, but I felt like I know you so well because this is one of my favorite books, The Code Breaker. And Walter Isaacson did such a wonderful job to tell your story. What did you think of the book?My interview with Walter Isaacson on The Code Breaker, a book I highly recommendJennifer Doudna (00:48):I thought Walter did a great job. He's a good storyteller, and as you know from probably from reading it or maybe talking to others about it, he wrote a page turner. He actually really dug into the science and all the different aspects of it that I think created a great tale.Eric Topol (01:07):Yeah, I recommended highly. It was my favorite book when it came out a couple years ago, and it is a page turner. In fact, I just want to read one, there's so many quotes out of it, but in the early part of the book, he says, “the invention of CRISPR and the plague of Covid will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery beginning just over a century ago, of the three fundamental kernels of our existence, the atom, the bit, and the gene.” That kind of tells a big story just in one sentence, but I thought I'd start with the IGI, the institute that you have set up at Berkeley and what its overall goals are.Jennifer Doudna (01:58):Right. Well, let's just go back a few years maybe to the origins of this institute and my thinking around it, because in the early days of CRISPR, it was clear that we were really at a moment that was quite unique in the sense that there was a transformative technology. It was going to intersect with lots of other discoveries and technologies. And I work at a public institution and my question to myself was, how can I make sure that this powerful tool is first of all used responsibly and secondly, that it's used in a way that benefits as many people as possible, and it's a tall order, but clearly we needed to have some kind of a structure that would allow people to work together towards those goals. And that was really the mission behind the IGI, which was started as a partnership between UC Berkeley and UCSF and now actually includes UC Davis as well.The First FDA Approved Genome EditingEric Topol (02:57):I didn't realize that. That's terrific. Well, this is a pretty big time because 10 years or so, I guess starting to be 11 when you got this thing going, now we're starting to see, well, hundreds of patients have been treated and in December the FDA approved the first CRISPR therapy for sickle cell disease, Casgevy. Is that the way you say it?Jennifer Doudna (03:23):Casgevy, yeah.Eric Topol (03:24):That must have felt pretty good to see if you go from the molecules to the bench all the way now to actually treating diseases and getting approval, which is no easy task.Jennifer Doudna (03:39):Well, Eric, for me, I'm a biochemist and somebody who has always worked on the fundamentals of biology, and so it's really been extraordinary to see the pace at which the CRISPR technology has been adopted, and not just for fundamental research, but also for real applications. And Casgevy is sort of the crowning example of that so far, is that it's really a technology that we can already see how it's being used to, I think it's fair to say, effectively cure a genetic disease for the first time. Really amazing.Genome Editing is Not the Same as Gene TherapyEric Topol (04:17):Yeah. Now I want to get back to that. I know there's going to be refinements about that. And of course, there's beta thalassemia, so we've got two already, and our mutual friend Fyodor Urnov would say two down 5,000 to go. But I think before I get to the actual repair of the sickle cell defect molecular defect, I think one of the questions I think that people listeners may not know is the differentiation of genome editing with gene therapy. I mean, as you know, there was recently a gene therapy approval for something like $4.25 million for metachromatic leukodystrophy. So maybe you could give us kind of skinny on how these two fundamental therapies are different.Jennifer Doudna (05:07):Right. Well, it's a great question because the terminology sounds kind of the same, and so it could be confusing. Gene therapy goes back decades, I can remember gene therapy being discussed as an exciting new at the time, direction back when I was a graduate student. That was little while ago. And it refers to the idea that we can use a genetic approach for disease treatment or even for a cure. However, it fundamentally requires some mechanism of integrating new information into a genome. And traditionally that's been done using viruses, which are great at doing that. It's just that they do it wherever they want to do it, not necessarily where we want that information to go. And this is where CRISPR comes in. It's a technology allows precision in that kind of genetic manipulation. So it allows the scientist or the clinician to decide where to make a genetic change. And that gives us tremendous opportunity to do things with a kind of accuracy that hasn't been possible before.Eric Topol (06:12):Yeah, no question. That's just a footnote. My thesis in college at University of Virginia, 1975, I'm an old dog, was prospects for gene therapy in man. So it took a while, didn't it? But it's a lot better now with what you've been working on, you and your colleagues now and for the last decade for sure. Now, what I was really surprised about is it's not just of course, these hemoglobin disorders, but now already in phase two trials, you've got hereditary angioedema, which is a life-threatening condition, amyloidosis, cancer ex vivo, and also chronic urinary tract infections. And of course, there's six more others like autoimmune diseases like lupus and type 1 diabetes. So this is really blossoming. It's really extraordinary.Eric Topol (07:11):I mean, wow. So one of the questions I had about phages, because this is kind of going back to this original work and discovery, antimicrobial resistance is really a big problem and it's a global health crisis, and there's only two routes there coming up with new drugs, which has been slow and not really supported by the life science industry. And the other promising area is with phages. And I wonder, since this is an area you know so well, why haven't we put more, we're starting to see more trials in phages. Why haven't we doubled down or tripled down on this to help the antimicrobial resistance problem?Jennifer Doudna (08:00):Well, it's a really interesting area, and as you said, it's kind of one of those areas of science where I think there was interest a while ago and some effort was made for reasons that are not entirely clear to me, at least it fizzled out as a real focused field for a long time. But then more recently, people have realized that there's an opportunity here to take advantage of some natural biology in which viruses can infect and destroy microbes. Why aren't we taking better advantage of that for our own health purposes? So I personally am very excited about this area. I think there's a lot of fundamental work still to be done, but I think there's a tremendous opportunity there as well.CRISPR 2.0Eric Topol (08:48):Yeah, I sure think we need to invest in that. Now, getting back to this sickle cell story, which is so extraordinary. This is kind of a workaround plan of getting fetal hemoglobin built up, but what about actually repairing, getting to fixing the lesion, if you will?Eric Topol (09:11):Yeah. Is that needed?Jennifer Doudna (09:13):Well, maybe it's worth saying a little bit about how Casgevy works, and you alluded to this. It's not a direct cure. It's a mechanism that allows activation of a second protein called fetal hemoglobin that can suppress the effect of the sickle cell mutation. And it's great, and I think for patients, it offers a really interesting opportunity with their disease that hasn't been available in the past, but at the same time, it's not a true cure. And so the question is could we use a CRISPR type technology to actually make a correction to the genetic defect that directly causes the disease? And I think the answer is yes. The field isn't there quite yet. It's still relatively difficult to control the exact way that DNA editing is occurring, especially if we're doing it in vivo in the body. But boy, many people are working on this, as you probably know. And I really think that's on the horizon.Eric Topol (10:19):Yeah. Well, I think we want to get into the in vivo story as well because that, I think right now it's so complicated for a person to have to go through the procedure to get ultimately this treatment currently for sickle cell, whereas if you could do this in vivo and you could actually get the cure, that would be of the objective. Now, you published just earlier this month in PNAS a wonderful paper about the EDVs and the lipid nanoparticles that are ways that we could get to a better precision editing. These EDVs I guess if I have it right, enveloped virus-like particles. It could be different types, it could be extracellular vesicles or whatnot. But do you think that's going to be important? Because right now we're limited for delivery, we're limited to achieve the right kind of editing to do this highly precise. Is that a big step for the future?Jennifer Doudna (11:27):Really big. I think that's gating at the moment. Right now, as you mentioned, somebody that might want to get the drug Casgevy for sickle cell disease or thalassemia, they have to go through a bone marrow transplant to get it. And that means that it's very expensive. It's time consuming. It's obviously not pleasant to have to go through that. And so that automatically means that right now that therapy is quite restricted in the patients that it can benefit. But we imagine a day when you could get this type of therapy into the body with a one-time injection. Maybe someday it's a pill that could be taken where the gene editors target the right cells in the body. In diseases like that, it would be the stem cells in the bone marrow and carry out gene editing that can have a therapeutic benefit. And again, it's one of those ideas that sounds like science fiction, and yet already there's tremendous advance in that direction. And I think over the next, I don't know, I'm guessing 5 to 10 years we're going to see that coming online.Editing RNA, the Epigenome, and the MicrobiomeEric Topol (12:35):Yeah, I'm guessing just because there's so much work on the lipid nanoparticles to tweak them. And there's four different components that could easily be made so much better. And then all these virus-like proteins, I mean, it may happen even sooner. And it's really exciting. And I love that diagram in that paper. You have basically every organ of the body that isn't accessible now, potentially that would become accessible. And that's exciting because whatever blossoming we're seeing right now with these phase two trials ongoing, then you basically have no limits. And that I think is really important. So in vivo editing big. Now, the other thing that's cropped up in recent times is we've just been focused on DNA, but now there's RNA editing, there's epigenetic or epigenomic editing. What are your thoughts about that?Jennifer Doudna (13:26):Very exciting as well. It's kind of a parallel strategy. The idea there would be to, rather than making a permanent change in the DNA of a cell, you could change just the genetic output of the cell and or even make a change to DNA that would alter its ability to be expressed and to produce proteins in the cell. So these are strategies that are accessible, again, using CRISPR tools. And the question is now how to use them in ways that will be therapeutically beneficial. Again, topics that are under very active investigation in both academic labs and at companies.Eric Topol (14:13):Yeah. Now speaking of that, this whole idea of rejuvenation, this is Altos. You may I'm sure know my friend here, Juan Carlos Belmonte, who's been pushing on this for some time at Altos now formerly at Salk. And I know you helped advise Altos, but this idea of basically epigenetic, well using the four Yamanaka factors and basically getting cells that go to a state that are rejuvenated and all these animal models that show that it really happens, are you thinking that really could become a therapy in the times ahead in patients for aging or particular ideas that you have of how to use that?Jennifer Doudna (15:02):Well, you mentioned the company Altos. I mean, Altos and a number of other groups are actively investigating this. Not I would say specifically regarding genome editing, although being able to monitor and probably change gene functions that might affect the aging process could be attractive in the future. I think the hard question there is which genes do we tweak and how do we make sure that it's safe? And better than me I mean, that's a very difficult thing to study clinically because it takes time for one thing, and we probably don't have the best models either. So I think there are challenges there for sure. But along the way, I feel very excited about the kind of fundamental knowledge that will come from those studies. And in particular, this question of how tissues rejuvenate I think is absolutely fascinating. And some organisms do this better than others. And so, understanding how that works in organisms that are able to say regrow a limb, I think can be very interesting.Eric Topol (16:10):And that gets me to that recent study. Well, as you well know, there's a company Verve that's working on the familial hypercholesterolemia and using editing with the PCSK9 through the liver and having some initial, at least a dozen patients have been treated. But then this epigenetic study of editing in mice for PCSK9 also showed results. Of course, that's much further behind actually treating patients with base editing. But it's really intriguing that you can do some of these things without having to go through DNA isn't it?Jennifer Doudna (16:51):Amazing, right? Yeah, it's very interesting.Reducing the Cost of Genome EditingEric Topol (16:54):Wild. Now, one of the things of course that people bring up is, well, this is so darn expensive and it's great. It's a science triumph, but then who can get these treatments? And recently in January, you announced a Danaher-IGI Beacon, and maybe you can tell us a bit about that, because again, here's a chance to really markedly reduce the cost, right?Jennifer Doudna (17:25):That's right. That's the vision there. And huge kudos to my colleague Fyodor Urnov, who really spearheaded that effort and leads the team on the IGI side. But the vision there was to partner with a company that has the ability to manufacture molecules in ways that are very, very hard, of course, for academic labs and even for most companies to do. And so the idea was to bring together the best of genome editing technology, the best of clinical medicine, especially focused on rare human diseases. And this is with our partners at UCSF and with the folks in the Danaher team who are experts at downstream issues of manufacturing. And so the hope there is that we can bring those pieces together to create ways of using CRISPR that will be cost effective for patients. And frankly, we'll also create a kind of roadmap for how to do this, how to do this more efficiently. And we're kind of building the plane while we're flying it, if you know what I mean. But we're trying to really work creatively with organizations like the FDA to come up with strategies for clinical trials that will maintain safety, but also speed up the timeline.Eric Topol (18:44):And I think it's really exciting. We need that and I'm on the scientific advisory board of Danaher, a new commitment for me. And when Fyodor presented that recently, I said, wow, this is exciting. We haven't really had a path to how to get these therapies down to a much lower cost. Now, another thing that's exciting that you're involved in, which I think crosses the whole genome editing, the two most important things that I've seen in my lifetime are genome editing and AI, and they also work together. So maybe before we get into AI for drug discovery, how does AI come into play when you're thinking about doing genome editing?Jennifer Doudna (19:34):Well, the thing about CRISPR is that as a tool, it's powerful not only as a one and done kind of an approach, but it's also very powerful genomically, meaning that you can make large libraries of these guide RNAs that allow interrogation of many genes at once. And so that's great on the one hand, but it's also daunting because it generates large collections of data that are difficult to manually inspect. And in some cases, I believe really very, very difficult to analyze in traditional ways. But imagine that we have ways of training models that can look at genetic intersections, ways that genes might be affecting the behavior of not only other genes, but also how a person responds to drugs, how a person responds to their environment and allows us to make predictions about genetic outcomes based on that information. I think that's extremely exciting, and I definitely think that over the next few years we'll see that kind of analysis coming online more and more.Eric Topol (20:45):Yeah, the convergence, I think is going to be, it's already being done now, but it's just going to keep building. Now, Demis Hassabis, who one of the brilliant people in the field of AI leads the whole Google Deep Mind AI efforts now, but he formed after AlphaFold2 behaving to predict proteins, 200 million proteins of the universe. He started a company Isomorphic Labs as a way to accelerate using AI drug discovery. What can you tell us about that?Jennifer Doudna (21:23):It's exciting, isn't it? I'm on the SAB for that company, and I think it's very interesting to see their approach to drug discovery. It's different from what I've been familiar with at other companies because they're really taking a computational lens to this challenge. The idea there is can we actually predict things like the way a small molecule might interact with a particular protein or even how it might interact with a large protein complex. And increasingly because of AlphaFold and programs like that, that allow accurate prediction of structures, it's possible to do that kind of work extremely quickly. A lot of it can be done in silico rather than in the laboratory. And when you do get around to doing experiments in the lab, you can get away with many fewer experiments because you know the right ones to do. Now, will this actually accelerate the rate at which we get to approved therapeutics? I wonder about your opinion about that. I remain unsure.Editing Out Alzheimer's Risk AllelesEric Topol (22:32):Yeah. I mean, we have one great success story so far during the pandemic Baricitinib, a drug that repurposed here, a drug that was for rheumatoid arthritis, found by data mining that have a high prospects for Covid and now saves lives in Covid. So at least that's one down, but we got a lot more here too. But it, it's great that Demis recruited you on the SAB for Isomorphic because it brings in a great mind in a different field. And it goes back to one of the things you mentioned earlier is how can we get some of this genome editing into a pill someday? Wow. Now, one of the things that for personal interest, as an APOE4 carrier, I'm looking to you to fix my APOE4 and give me APOE2. How can I expect to get that done in the near future?Jennifer Doudna (23:30):Oh boy. Okay, we'll have to roll up our sleeves on that one. But it is appealing, isn't it? I think about it too. It's a fascinating idea. Could we get to a point someday where we can use genome editing as a prophylactic, not as a treatment after the fact, but as a way to actually protect ourselves from disease? And the APOE4 example is a really interesting one because there's really good evidence that by changing the type of allele that one has for the APOE gene, you can actually affect a person's likelihood of developing Alzheimer's in later life. But how do we get there? I think one thing to point out is that right now doing genome editing in the brain is, well, it's hard. I mean, it's very hard.Eric Topol (24:18):It a little bit's been done in cerebral spinal fluid to show that you can get the APOE2 switch. But I don't know that I want to sign up for an LP to have that done.Jennifer Doudna (24:30):Not quite yet.Eric Topol (24:31):But someday it's wild. It's totally wild. And that actually gets me back to that program for coronary heart disease and heart attacks, because when you're treating people with familial hypercholesterolemia, this extreme phenotype. Someday and this goes for many of these rare diseases that you and others are working on, it can have much broader applicability if you have a one-off treatment to prevent coronary disease and heart attacks and you might use that for people well beyond those who have an LDL cholesterol that are in the thousands. So that's what I think a lot of people don't realize that this editing potential isn't just for these monogenic and rare diseases. So we just wanted to emphasize that. Well, this has been a kind of wild ride through so much going on in this field. I mean, it is extraordinary. What am I missing that you're excited about?Jennifer Doudna (25:32):Well, we didn't talk about the microbiome. I'll just very briefly mention that one of our latest initiatives at the IGI is editing the microbiome. And you probably know there are more and more connections that are being made between our microbiome and all kinds of health and disease states. So we think that being able to manipulate the microbiome precisely is going to open up another whole opportunity to impact our health.Can Editing Slow the Aging Process?Eric Topol (26:03):Yeah, I should have realized that when I only mentioned two layers of biology, there's another one that's active. Extraordinary, just going back to aging for a second today, there was a really interesting paper from Irv Weissman Stanford, who I'm sure you know and colleagues, where they basically depleted the myeloid stem cells in aged mice. And they rejuvenated the immune system. I mean, it really brought it back to life as a young malice. Now, there probably are ways to do that with editing without having to deplete stem cells. And the thought about other ways to approach the aging process now that we're learning so much about science and about the immune system, which is one of the most complex ones to work in. Do you have ideas about that are already out there that we could influence the aging process, especially for those of us who are getting old?Jennifer Doudna (27:07):We're all on that path, Eric. Well, I guess the way that I think about it is I like to think that genome editing is going to pave the way to make those kinds of fundamental discoveries. I still feel that there's a lot of our genetics that we don't understand. And so, by being able to manipulate genes precisely and increasingly to look at how genes interact with each other, I think one fundamental question it relates to aging actually is why do some of us age at a seemingly faster pace than others? And it must have to do at least in part with our genetic makeup and how we respond to our environment. So I definitely think there are big opportunities there, really in fundamental research initially, but maybe later to actually change those kinds of things.Eric Topol (28:03):Yeah, I'm very impressed in recent times how much the advances are being made at basic science level and experimental models. A lot of promise there. Now, is there anything about this field that you worry about that keeps you up at night that you think, besides, we talked about that we got to get the cost down, we have to bridge health inequities for sure, but is there anything else that you're concerned about right now?Jennifer Doudna (28:33):Well, I think anytime a new technology goes into clinical trials, you worry that things may get out ahead of their skis, and there may be some overreach that happens. I think we haven't really seen that so far in the CRISPR field, which is great. But I guess I remain cautious. I think that we all saw what happened in the field of gene therapy now decades ago, but that really put a poll on that field for a long time. And so, I definitely think that we need to continue to be very cautious as gene editing continues to advance.Eric Topol (29:10):Yeah, no question. I think the momentum now is getting past that point where you would be concerned about known unknowns, if you will, things that going back to the days of the Gelsinger crisis. But it's really extraordinary. I am so thrilled to have this conversation with you and to get a chance to review where the field is and where it's going. I mean, it's exploding with promise and potential well beyond and faster. I mean, it takes a drug 17 years, and you've already gotten this into two treatments. I mean, I'm struck when you were working on this, how you could have thought that within a 10-year time span you'd already have FDA approvals. It's extraordinary.Jennifer Doudna (30:09):Yeah, we hardly dared hope. Of course, we're all thrilled that it went that fast, but I think it would've been hard to imagine it at the time.Eric Topol (30:17):Yeah. Well, when that gets simplified and doesn't require hospitalizations and bone marrow, and then you'll know you're off to the races. But look, what a great start. Phenomenal. So congratulations. I'm so thrilled to have the chance to have this conversation. And obviously we're all going to be following your work because what a beacon of science and progress and changing medicine. So thanks and give my best to my friend there at IGI, Fyodor, who's a character. He's a real character. I love the guy, and he's a good friend.Jennifer Doudna (30:55):I certainly will Eric, and thank you so much. It's been great talking with you.*******************************************************Thanks for listening and/or reading this edition of Ground Truths.I hope you found it as stimulating as I did. Please share if you did!A reminder that all Ground Truths posts (newsletter and podcast( are free without ads. Soon we'll set it up so you can select what type of posts you want to be notified about.If you wish to be a paid subscriber, know that all proceeds are donated to Scripps Research, and thanks for that—it greatly helped fund our summer internship program for 2023 and 2024.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio/video support. Get full access to Ground Truths at erictopol.substack.com/subscribe

Max Jaderberg, Director of Machine learning at Isomorphic labs, shares the Isomorphic approach to drug discovery in one of their first interviews as they emerge from shadow mode. In 2020 Google DeepMind made history when they took on the grand challenge of biology- the protein folding problem- with their algorithm AlphaFold2.  Their success prompted the creation of a sister company, Isomorphic Labs. Our conversation topics include:   - The concept of “Digital Biology”- How AI can be used model the biological world  - Bottlenecks in the drug discovery process and how AI could circumvent them - How AI may unlock 'undraggable targets' to find treatments for incurable diseases  Links: Isomorphic labs website: https://www.isomorphiclabs.com/ AlphaMissence: https://www.deepmind.com/blog/alphamissense-catalogue-of-genetic-mutations-to-help-pinpoint-the-cause-of-diseases

Global Policy Watch: Chronicle Of A Crisis Foretold Reflections on global policy issues — RSJA major state election (Karnataka) is coming up this week. But there's hardly anything worth analysing. The Congress seemed to have a slight edge in the early opinion polls, but that's wearing thin. The BJP, always with its ears to the ground, has cranked up its poll machinery in the last couple of weeks drawing upon the star power of the PM in the urban areas of the state. The friendly media houses have been mobilised to pick up ‘emotive' issues that would tilt the scale in favour of the party in power. It is not too difficult to figure out what the average voter wants if you go by the opinion polls and surveys. But those substantive issues just don't feature in the public discourse. If you read the papers or media reports on what's being debated among parties in Karnataka, it is about who is a Hindu hater, who prostrates more often before deities and how going back to the OPS (old pension scheme) is such a wonderful idea. In the classical model of how representative democracy ought to work, the voters would have a limited view of how the world works, and it is the representative who owes the voters not only his labour but also his judgment on issues (to riff on Burke). That seems to be inverted here. One set of representatives has, over the last few years, instituted all kinds of targeted laws - hijaab ban, anti-conversion laws, scrapping minority quotas and cow slaughter ban - in the hope that they will yield electoral gains. The other set is talking of another set of bans convenient to them and some really bad economic policies. We often say that this newsletter attempts to change the demand side of the political equation by making people more aware of public policies and demanding better from their representatives. What we have here is the public demanding the right kind of things (if opinion polls are to go by), but their representatives are keen on dragging them back to divisive emotive issues. The Karnataka election will be a good test of what prevails eventually. I can almost see the straight line from these polls to the general elections due almost exactly 12 months from now. We will all be debating similar trivial issues than what really should matter to India. For some reason, that doesn't make for a good topic of debate. It makes any election analysis a waste of time, really. Switching gears, as I finished writing my last week's edition on what the US Fed refuses to learn from the SVB collapse, another mid-sized US bank, the First Republic Bank (FRB), went down and was sold to J.P. Morgan, the ultimate backstop in the US financial system. No amount of assurance from FDIC to the depositors of the bank nor the combined infusion of capital about a month back from a consortium of big banks into FRB was enough to stanch the outflow of deposits. Soon the bank was insolvent, the shareholders and bondholders lost everything, and J.P. Morgan was given enough of a sweet deal to pick up the pieces. I'm sure the Fed will come out with another report on the FRB collapse where it will blame the management for not hedging its treasury risks and being lax in its risk practices. There will be a light rap to the supervisors and staff from Fed who monitored FRB, and that will be that. I hope there's some more introspection by the Fed than that. Because as the shares of PacWest and Western Alliance have sunk over the last two days, it is clear that a number of mid-sized banks are going to collapse in slow-motion and end up in the lap of J.P. Morgan or FDIC very soon. The feeble Fed response was a 25 bps hike in rates last week with a strong indication that it will hit the pause button on hikes now. The question is if that's enough to structurally save many of these banks.I have argued for the past couple of months (just after the SVB collapse) that there are three problems for the Fed to contend with, and there are no real answers for them. It is Hail Mary time. Choose the best among the worst options and brace for the impact. I will lay out the three problems it faces before suggesting what looks like the best of the worst option that the Fed has chosen. First, the Fed continued raising interest rates to fight inflation without thinking through its impact on the banking system. This much is clear now. The surprises that have come up in the shape of SVB, Signature and FRB weren't anticipated at all. As the interest rates rose, the value of the long-term assets held by banks has fallen while their liabilities, in the form of deposits, which tend to be shorter in term, haven't fallen as much. The slowdown in the economy has meant there's not enough demand for credit at elevated rates, which means banks continue to invest in long-term US treasury bills. Every time the rates go up, these held-to-maturity (HTM) assets take a notional mark-to-market loss. A recent report by the Hoover Institution suggests that at this moment, the US Banking system's market value of assets is about $ 2 trillion below their book value. In an article on Yahoo Finance, Ambrose Evan-Pritchards writes:The second and third biggest bank failures in US history have followed in quick succession. The US Treasury and Federal Reserve would like us to believe that they are “idiosyncratic”. That is a dangerous evasion.Almost half of America's 4,800 banks are already burning through their capital buffers. They may not have to mark all losses to market under US accounting rules but that does not make them solvent. Somebody will take those losses.“It's spooky. Thousands of banks are underwater,” said Professor Amit Seru, a banking expert at Stanford University. “Let's not pretend that this is just about Silicon Valley Bank and First Republic. A lot of the US banking system is potentially insolvent.”The second problem, which kind of starts giving this a contagion feel, is the state of the commercial property market in the US. Interest rates have moved up too fast, the slowdown is real with many large employers laying off people, so there's no real need for commercial capacity, and the excess liquidity fuelled by the Fed during the pandemic meant additional capacity was built up cheaply, which now has no takers. What's worse, the rapid increase in rates means that a lot of these loans that will come up for refinancing soon (at higher rates) will face defaults. The mid-sized regional banks have a sizable exposure to commercial real estate, with estimates that about two-thirds of all commercial property borrowing comes from them. From the same Yahoo Finance article:Packages of commercial property loans (CMBS) are typically on short maturities and have to be refinanced every two to three years. Borrowing exploded during the pandemic when the Fed flooded the system with liquidity. That debt comes due in late 2023 and 2024.Could the losses be as bad as the subprime crisis? Probably not. Capital Economics says the investment bubble in US residential property peaked at 6.5pc of GDP in 2007. The comparable figure for commercial property today is 2.6pc.But the threat is not trivial either. US commercial property prices have so far fallen by just 4pc to 5pc. Capital Economics expects a peak to trough decline of 22pc. This will wreak further havoc on the loan portfolios of the regional banks that account for 70pc of all commercial property financing.Estimates vary, but it is likely that even a 10-15 per cent increase in default rates on commercial property when the refinancing chickens come home to roost could mean about $ 100 billion in losses for banks. And these are real losses, not the notional variety sitting on the books. Will the regional banks be able to weather this? And what happens if 4-5 of them catch a cold together in this portfolio? The risk of contagion flowing up the banking food chain is real.Lastly, the Fed, FDIC and the government took the extraordinary step of guaranteeing all deposits after the collapse of SVB to reassure depositors and not have further runs on mid-sized banks. But that didn't stop the ever-increasing deposit erosion for FRB during April. People can do the math, and they realise there's no way the government can fill a giant hole in case there's a real deposit run. The FDIC, after all, has a little over $ 100 billion to act as insurance for such an eventuality. That's loose change in the broader scheme of things. So, the depositors will flee the more you try and convince them all's well. Plus, the blanket deposit backstop has meant there's a moral hazard built right there for the management not to be too worried about the nature of deposits they bring or the risk of serious asset-liability mismatches. At the time of SVB collapse, I wrote in edition # 205:I guess one way to look at this is if you let fiscal dominance become the central canon of how you manage your economic policy, you will eventually reach the same place as other economies (mostly developing) that have indulged in the same for years. The monetary authorities in the U.S. have been accommodating the fiscal profligacy of the treasury for years. This was accentuated during the pandemic. Trillions of dollars were pumped in to save the economy. I'm not sure how much the economy needed saving then. But that bill has come now. First in the shape of inflation, followed by rapid, unprecedented rate hikes and the inevitable accidents that are showing up now. Almost certainly, a recession will follow. Isomorphic mimicry of Latin American monetary policy indeed.Now, back to Evans-Pritchard and his article in Yahoo Finance:The root cause of this bond and banking crisis lies in the erratic behaviour and perverse incentives created by the Fed and the US Treasury over many years, culminating in the violent lurch from ultra-easy money to ultra-tight money now underway. They first created “interest rate risk” on a galactic scale: now they are detonating the delayed timebomb of their own creation.Chris Whalen from Institutional Risk Analyst said we should be wary of a false narrative that pins all blame on miscreant banks. “The Fed's excessive open market intervention from 2019 through 2022 was the primary cause of the failure of First Republic as well as Silicon Valley Bank,” he said.Mr Whalen said US banks and bond investors (i.e. pension funds and insurance companies) are “holding the bag” on $5 trillion of implicit losses left by the final blow-off phase of the Fed's QE experiment. “Since US banks only have about $2 trillion in tangible equity capital, we have a problem,” he said.Going back to the original question I posed - what will Fed do given these problems on hand? I guess it has decided to choose what it thinks is the least worst option. It cannot let go of its fight against inflation. It has to find a way to avoid recession. So, all it can afford is a controlled banking crisis. An oxymoron if ever there was one. But that's where we are headed, where we will see things unfold in a slow but almost predictable manner. The Fed will try and boost the banks' capital in the meantime and hope the best of them brave through this without any risk of contagion. Anyway, in the worst case, there's always Jamie Dimon and his chequebook.Thanks for reading Anticipating the Unintended! Subscribe for free to receive new posts and support our work.Numbers that Ought to Matter: In April 2023, the Union Health Minister reported that India has 108,000 MBBS seats in 660 colleges and 118,000 BSc nursing seats in approx 900 colleges. The total number of seats on offer is quite low, despite the large number of colleges. On average, each medical college has 163 seats, and each nursing college has just 131 seats. Government policy should focus on helping existing colleges increase their intake. For more context, read edition #159.India Policy Watch #1: Coal is Out? Naah.Insights on issues relevant to India— Pranay KotasthaneEarlier this week, I came across this Business Standard report:“India plans to stop building new coal-fired power plants, apart from those already in the pipeline, by removing a key clause from the final draft of its National Electricity Policy (NEP), in a major boost to fight climate change, sources said.”My prior assumption was that given coal-based power's lower costs, India would construct many more coal-powered plants over the next two decades to meet a growing economy's demand. Hence, this news item came as a bit of a surprise. So I went through the draft National Electricity Plan to understand the reasoning.Before we dive in, some bureaucratic knots that need untangling. The cited “final draft” of the National Electricity Policy is nowhere to be found on the Ministry of Power website. But I could find an earlier draft on the IIT Kanpur's Centre for Energy Regulation website! A Policy document such as this only lists the priorities and steers the sector. From it arises a Plan that's to be released every five years by the Central Electricity Authority. The Plan document is the real deal as it does demand projections through an ‘Electric Power Survey'. It then presents the energy generation mix required to meet the projected demand scenarios. A part of this elusive plan document was released, after many delays, in September 2022. Some relevant insights from the plan:* The current installed power capacity of ~400GW split looks as follows:* By FY32, it is projected that India's energy demand will be 2538 Billion Units, and peak power demand will be 363 GW, up from 1624 Billion Units and peak demand of 216 GW in FY23. * Coal+Lignite accounted for 52.7% of total installed capacity in FY23.* Using a planning tool that optimises for factors such as fuel availability, operational availability, and sustainability, the Plan throws up a required power generation capacity mix.* After taking all these constraints into account, the Plan finds that by FY32, India would need an additional installed coal capacity of 42.6 GW in the base case scenario and 53.6 GW in the increased-demand scenario. * Around 25.6 GW of capacity addition is already in various stages of execution.Now, we come to the report claiming a ban on additional coal capacity addition beyond the current in-progress projects. It essentially means that to meet the projected demand, India will have to find other sources to compensate for coal. In the best case, an additional 17 GW capacity will have to be conjured up; and in the worst-case scenario, nearly 28 GW capacity will have to be compensated. This additional capacity goes beyond the planned additions in clean energy generation. That's why I am sceptical about this news report. It's unlikely that government will make a blanket commitment.If we assume the report to be true, advancing the date of halting further coal power generation will require compensation by another reliable source to provide the base load. Only two options can be imagined with today's technology — nuclear energy and Battery Energy Storage Systems (BESS).Nuclear energy accounts for just 2 per cent of the total power generation mix today. The current plan already assumes a threefold increase in nuclear power capacity addition. For it to absorb the slack of stopping further coal addition, it has to reach six to eight times the current capacity. Given that nuclear power generation faces the problem of high capital costs and invites protests, scaling it up is tough unless the Small Modular Reactor (SMR) technology breakthrough leads to mass adoption in India. Maybe for this reason, the government is “considering” overturning a ban on FDI in nuclear power. Expanding BESS capacity also depends on the ability to develop Lithium refining expertise and bring other options, such as Sodium-ion batteries, online. So, stopping the building of new coal-fired power plants requires far too many other pieces of the puzzle to fall into place. Keep watching this space.Tailpiece: check out this Puliyabaazi episode on the chemistry, geopolitics, and significance of Lithium-ion batteries.India Policy Watch #2: Lessons from Apple's India Journey Thus FarInsights on issues relevant to India— Pranay KotasthaneApple's quarterly results are out. Its India revenue registered double-digit growth, prompting Tim Cook to make the now-commonplace “India is at a tipping point” statement. The last seven years have been stunning for Apple's India business. From being shunned away by the government for their plan to import and sale of refurbished phones to becoming a poster child of electronics manufacturing in India, Apple's India strategy has come a long way.I've always wanted to know how Apple raised its India game and whether there are broader lessons for Indian public policy from this experience. So I was delighted to read Surajeet Das Gupta's Business Standard article narrating Apple's tryst with Indian public policy. Das Gupta identifies these milestones and speed-breakers:* In 2016, after denying the import-refurbish-sell request, Apple was told to start manufacturing in India if it wanted to set up Apple-owned retail stores.* In 2017, Apple put forward two pre-conditions for starting manufacturing in India:* “15-year duty concessions (on capital equipment, components, consumables for smartphones).. and a reduction in customs duty on completely knocked down and semi-knocked down devices to be assembled in India.” * relaxation of 30 per cent local sourcing directive for foreign direct investment (FDI) in single-brand retail stores.* After both its asks were rejected, it set up an India team to work with the government and mobile phone industry associations.* After three years of lobbying, the government relented by allowing the 30 per cent local norm to be met as an average for the first five-year period, not annually. Then the government agreed to qualify the value added by Apple's contract manufacturers in India—regardless of the destination of these products—as “local sourcing”.* The government allowed Apple to set up an online store before the physical store if it brought over $200 million FDI and extracted a commitment that the online store couldn't get into heavy discounting.* When PLI rules were modified to accommodate Samsung's entry, Apple went along with the change.* After the government made the entry of FDI from China in the Indian tech sector arduous due to the Galwan clash, Apple worked with the industry body to get 12 of its Chinese suppliers approved on the condition that they would enter into joint ventures with Indian partners who would have a majority stake. (We wrote about it in edition #199).Take a breath. And it has only been seven years. There are three ways of interpreting this journey from a public policy perspective.First, to the extent that the government has been able to capture Apple's China manufacturing—even if in a really small way—its approach can be called a limited success. The government can rightfully claim that Apple's supply chain has created over a lakh jobs in India. Grabbing some part of the manufacturing of the world's biggest company has a signalling effect as well. It will also help Apple's Indian partners upgrade technologically and raise their standards. Second, Apple's up-and-down journey also serves as a warning. If the world's most well-known company had to jump as many hoops, what chance does a smaller company have? How many other businesses will have the money and patience to set up India teams that negotiate with the government to remove roadblocks, one by one, calmly? And the approval of Apple's Chinese suppliers shows that the government is comfortable making pro-business exemptions but is uncomfortable making pro-market relaxations. There's a risk of going overboard with the “market access in return for manufacturing” approach. A policy analyst must also pop the opportunity cost question. Could the government have spent precious state capacity elsewhere by following a general easing of these constraints? How many companies did India lose in the process of playing hardball with Apple? And what about the Indian consumers - what did they lose as a result of these overbearing conditions? These are tough questions to answer.Third, this journey shows that technology policy is shaping up rather well in India. Industry associations and public advocacy departments of companies are now able to put forward their demands and grouses in front of governments in a far more transparent manner. Not just that, they are able to get governments to modify policies as well.In my view, all three interpretations are simultaneously true. But this is just the beginning of India's electronics manufacturing journey. The steps required to strengthen it might be drastically different from the approach required to start it.HomeWorkReading and listening recommendations on public policy matters* [Article] Here's a RestofWorld Q&A on the US-China chip war and its implications for India featuring one of us.* [Story] FT has an excellent visual explainer on quantum computing this week.* [Article] Niranjan Rajadhyaksha's Mint column comparing Asian countries when their median age was 28 like India's is today, is insightful. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit publicpolicy.substack.com

Global Policy Watch: Bailout Pe Bailout Pe BailoutInsights on global policy issues relevant to India— RSJWhere do I start this week? Maybe with a spot of self-promotion. Pranay and I were guests on the popular Hindi podcast Puliyaabazi. I have been a long-time fan, so it was nice to be a guest there. Pranay usually co-hosts this with Saurabh and Khyati, but this time, he was on the other side. I felt a bit like Uday Chopra, who is only in the film because he is the producer's brother. Anyway, I think a good time was had by all as we covered a wide variety of topics - Enlightenment and why it didn't happen in India (short answer: there wasn't any need, really), why we write this newsletter (majboori) and the usual quota of Bastiat, Smith and Rorty (showing off). Do listen if you have time (of course, you do).Moving on. Here is a quick run-through of what's gone on since my last post. Another US regional bank, Signature Bank, stared into the abyss with depositors making a run to withdraw their money as analysts looked around for large unrealised losses sitting on banks' balance sheets. Fed officials spent their weekend hawking the other failed bank, Silicon Valley Bank (SVB), to potential buyers. But who in their right mind will buy out a troubled bank in these times? More so after all the trouble that the likes of JP Morgan Chase had buying out such banks during the financial crisis of 2009. Running out of options, the Fed, the Treasury and the Federal Deposit Insurance Corporation (FDIC) announced an unprecedented bailout of all depositors of SVB and any other bank that will be in a similar hole in future. Simply put, FDIC will guarantee all deposits and not just those below $250,000 for which there's insurance. To be sure, the equity shareholders and those holding unsecured corporate bonds won't be bailed out. They will lose their shirts. So, this isn't a repeat of the 2009 bailouts. The Fed then went a step further to address the root cause of the problem. Banks are sitting on huge held-to-maturity (HTM) losses on the securities they hold because the interest rates have moved too far up too quickly. And they have a liquidity issue if there are continued withdrawals from the depositors. If they sell their securities today to meet their commitments to give depositors their money when they ask for it, they will have to sell them at a loss. This substantial loss will mean they will need to raise capital from shareholders to keep themselves solvent as per Fed requirements. But who will give them money in this market? Uninsured depositors who play out this game-theory scenario in their minds will therefore withdraw more of their money. Ideally, if they play the scenario right as a collective, they shouldn't. But as individuals, they will make a run on the bank. Soon, the bank will be in a death spiral, and this is what happened at SVB and Signature Banks. The last-minute solution devised by Fed was the creation of what's termed the Bank Term Funding Program (BTFP). Here's how Fed sees BTFP:“The additional funding will be made available through the creation of a new Bank Term Funding Program (BTFP), offering loans of up to one year in length to banks, savings associations, credit unions, and other eligible depository institutions pledging U.S. Treasuries, agency debt and mortgage-backed securities, and other qualifying assets as collateral. These assets will be valued at par. The BTFP will be an additional source of liquidity against high-quality securities, eliminating an institution's need to quickly sell those securities in times of stress.With approval of the Treasury Secretary, the Department of the Treasury will make available up to $25 billion from the Exchange Stabilization Fund as a backstop for the BTFP. The Federal Reserve does not anticipate that it will be necessary to draw on these backstop funds.”If you didn't have any background to this situation and just read the above note from the Fed, you'd be forgiven if you thought here was a central bank of a developing world economy figuring out a short-term jugaad to solve a crisis at hand. But the Fed didn't just stop here. After all, like the Queen in Through The Looking Glass, it can believe in six impossible things before breakfast. Leaving their struggles to find a buyer for Signature Bank behind, they put together a unique Barjatya style “hum saath saath hain” deal and nudged a number of banks to do their bit to shore up confidence in the banking system: (as CNBC reports)“A group of financial institutions has agreed to deposit $30 billion in First Republic in what's meant to be a sign of confidence in the banking system, the banks announced Thursday afternoon.Bank of America, Wells Fargo, Citigroup and JPMorgan Chase will contribute about $5 billion apiece, while Goldman Sachs and Morgan Stanley will deposit around $2.5 billion, the banks said in a news release. Truist, PNC, U.S. Bancorp, State Street and Bank of New York Mellon will deposit about $1 billion each.“This action by America's largest banks reflects their confidence in First Republic and in banks of all sizes, and it demonstrates their overall commitment to helping banks serve their customers and communities,” the group said in a statement.“This show of support by a group of large banks is most welcome, and demonstrates the resilience of the banking system,” The Federal Reserve, Treasury Department, Federal Deposit Insurance Corporation and Office of the Comptroller of the Currency said in a joint statement.”Remind me now, sometime in the past, I have accused Indian policymakers of what's called isomorphic mimicry. It is a concept developed by Lant Pritchett et al to explain the tendency of governments to mimic other governments' successes, replicating processes, systems, and even products of the “best practice” examples without actually developing the functionality of the institutions they are imitating. Policymaking in developing countries often falls prey to this. A good example of this is imitating the green energy policies implemented in Sweden (a $60,000 per capita economy) in India (a $2000 per capita economy) which has neither the state capacity to implement nor the public readiness to accept such policies. Why am I bringing up isomorphic mimicry here? Well, because I never imagined a day shall dawn when the US policymakers take a leaf out of what India did when faced with a crisis. What the Fed did to save Signature Bank is isomorphic mimicry flowing the other way. To refresh your memory, here's a Business Standard report (Mar 13, 2020) on what the Finance Ministry and RBI did to save Yes Bank in 2020:“Hours after the Cabinet approved reconstruction scheme for YES Bank, private lenders ICICI Bank, HDFC, Kotak Mahindra Bank and Axis Bank came to the cash-strapped bank's rescue. While the SBI had earlier announced its decision to purchase 49 per cent shares, both ICICI Bank and HDFC are set to invest Rs 1000 crore each with Axis Bank pouring Rs 600 crore to pick up 60 crore shares of the troubled lender and Kotak Mahindra infusing an equity capital of Rs 500 crore under the RBI's bailout plan.The developments took place soon after Finance Minister Nirmala Sitharaman said that other investors were also being invited.”I guess one way to look at this is if you let fiscal dominance become the central canon of how you manage your economic policy, you will eventually reach the same place as other economies (mostly developing) that have indulged in the same for years. The monetary authorities in the U.S. have been accommodating the fiscal profligacy of the treasury for years. This was accentuated during the pandemic. Trillions of dollars were pumped in to save the economy. I'm not sure how much the economy needed saving then. But that bill has come now. First in the shape of inflation, followed by rapid, unprecedented rate hikes and the inevitable accidents that are showing up now. Almost certainly, a recession will follow. Isomorphic mimicry of Latin American monetary policy indeed. Anyway, that was not the only bailout of the week. We also had Credit Suisse almost going under in a bad case of deja vu to those who have seen 2009. Here's CNBC on this:“Credit Suisse announced it will be borrowing up to 50 billion Swiss francs ($53.68 billion) from the Swiss National Bank under a covered loan facility and a short-term liquidity facility.The decision comes shortly after shares of the lender fell sharply Wednesday, hitting an all-time low for a second consecutive day after its top investor Saudi National Bank was quoted as saying it won't be able to provide further assistance. The latest steps will “support Credit Suisse's core businesses and clients as Credit Suisse takes the necessary steps to create a simpler and more focused bank built around client needs,” the company said in an announcement.In addition, the bank is making a cash tender offer in relation to ten U.S. dollar denominated senior debt securities for an aggregate consideration of up to $2.5 billion – as well as a separate offer to four Euro denominated senior debt securities for up to an aggregate 500 million euros, the company said.”What's that word that starts with C and was used a lot during the pandemic? Well, that C word is knocking at the doors of global finance right now. It is not a contagion yet. But the odds of it happening have significantly gone up in the past week.I will close this by covering the two discussion themes emerging from these events. First, what happens to the hawkish stance the Fed had taken a couple of weeks back on more rapid rate hikes in the light of inflation being sticky and inflation expectations being anchored? This, as I have written earlier, is of real interest to India and its policymaking stance. The Fed is in an absolute bind now before its meeting on Wednesday to take a call on rates. A rate hike in the current environment will make the weak banks look even more vulnerable despite the deposit backstop and the additional liquidity available from BTFP. And who knows what other accidents are lurking that will show up as the rates go higher? Does the Fed want to risk financial instability? On the other hand, inflation is real, and it is an election year. Runaway inflation will mean the eventual taming of it, and the recession that will follow will be hard and long. Who wants to preside over that? I see almost zero chance of a rate hike in this cycle. The Fed might wait till May to resume raising rates after it has weathered this risk of banking contagion and waiting for the April inflation data. But even then, the core problem remains. Further rate hikes will expose weak players, and that will mean we will have accidents. So long as they are small and contained, it is worth the risk of raising rates. But who can predict the nature of the accidents?Second, there's some kind of war that's broken out on social media on who is responsible for the collapse of SVB and Signature. There are those who believe it is the Fed whose actions over the past three years are solely responsible for the situation we are in now. The crux of the argument is that the Fed forecasts the interest rate and then it sets the rate. Banks take bets on long-term securities based on these forecasts. This is called duration risk. If the Fed then sets the rate that's so far removed from their own forecasts, what do poor treasury folks in Banks do? Plus, it is the Fed that has been making the rules since the GFC to direct a whole lot of bank liquidity into the purchase of long-term government bonds. The whole system is rigged by the Fed, and when things go wrong, it cannot pontificate on the risk management practices of banks. The counter to this is that the Fed only puts out an interest forecast based on the data (esp on inflation) that's available. When the incoming data changes, its forecast changes. This deviation is in a narrow band in usual times. In unusual times like what we've been through in the past two years, you may have a bigger variance. Banks have multiple ways to hedge duration risks. Instead of looking at the Fed to apportion blame, one should look at how conveniently the depositors of SVB - the VCs, startups and other cool people - jumped ship at the first sign of trouble when they know such a collective deposit withdrawal will make the situation worse. It is incredibly stupid of this deposit base that prides itself on its ability to see further, take long-term bets and dimension risks better than others, that it could not have the patience to stand by a bank that has served them well. The problem of SVB bank, according to this lot, is they were over-reliant on a lopsided deposit base, and that deposit base acted most stupidly. I think both these debates are going to rage on for some time. The Fed has slipped down the path where it has allowed fiscal dominance to overrule prudent policymaking. It is quite difficult to retrieve ground from there unless you have a Fed Chair with the intellectual heft and drive to restore balance. Equally, asset liability matching (ALM) is a core responsibility of banks. They are supposed to diversify their base of customers, monitor duration risks, and stress-test their balance sheet. All the strutting around as a cool disruptive bank or hanging out with your clients should not distract you from that fundamental truth. You take your eye off it, you veer off the road.    Advertisement: Admissions to Takshashila's Post-graduate Programme in Public Policy (PGP) are now open. This is a fantastic opportunity if you want to dive deep into public policy while pursuing your work responsibilities.India Policy Watch: Milking Consumers and Producers, All at OnceInsights on burning policy issues in India— Pranay KotasthaneWe harp on Hayek's paper, The Use of Knowledge in Society, in this newsletter. Price is a vital signal, a decentralised coordination mechanism between producers and consumers. And so, when governments prohibit its functioning, bizarre things happen. Let's analyse the consequences of price distortion using an ongoing situation — the milk shortage in Karnataka. A bit of background to set things up. Milk is an ‘essential' commodity. Its essentiality is not just a matter of fact or reason but also a carte blanche for Indian governments to regulate the production, supply, and distribution of any commodity that is classified as essential under the Essential Commodities Act (ECA), 1955. In practical terms, it means that the government fixes procurement prices, caps consumer prices, and often owns and runs everything that lies between these the producer and the consumer.So is the case with milk in most states, including Karnataka. The Karnataka Milk Federation (KMF) is a dairy cooperative under the Department of Cooperation, Government of Karnataka. It procures nearly 50 per cent of all the milk that is produced in the state. It sells products under the brand name Nandini. Nearly 50 per cent of its consumption happens in the capital, Bengaluru. Government ownership complicates and comicalises the situation in a way that can only be equalled by a Priyadarshan comic flick. See, for instance, what has happened due to a milk supply chain disruption over the last few weeks. As the summer began early this year, the demand for milk rose sharply. A glass of majjige (buttermilk) or lassi is a wonderful refresher in the heat. Simultaneously, the supply drops in the summer months. Natural adaptation dictates that animals produce less milk than usual in the heat. A bout of lumpy skin disease has further exacerbated the gap between demand and supply this year. For an ordinary product, a rise in prices would iron out this demand-supply gap quickly. With an increase in prices, consumers will rationalise consumption, while the producers will work harder to increase the supply. But when governments own the supply chain, price rises are defenestrated, and a chain of bizarre events emerges.First, electoral concerns circle over pricing decisions like vultures. In this particular case, the government will not touch the price caps with a barge pole because the Karnataka elections are due in May. So the government tries to increase prices in a roundabout way: increase the maximum retail price (MRP) but offer a reduced quantity of milk for the same packet price.Second, shortages abound. Since the administered price rises have not done enough to make the demand-supply gap go away, milk shortages have emerged. The rich can well afford to buy premium milk at higher prices from other suppliers. But for the poor, the milk packets disappear. Instead of paying a slightly higher price until the supply rises again, the less-privileged consumers are left only with an empty glass.Third, the government resorts to blaming private businesses. Someone has to be blamed, and as so often happens in India, businesses get the flak. See this report in The Hindu, which casually places the blame on private players who are now willing to offer higher prices to the dairies and farmers. The report says:“Private players purchasing milk from the retail market to sustain their businesses in milk products is said to be causing a disruption…“He also said private dairies were procuring milk directly from farmers in rural areas by offering a higher price, thus reducing the union's procurement.”We should have been celebrating private players that are offering a better deal to farmers, given the scarcity. Instead, they have become villains. And fourth, a quotidian issue becomes a front for inter-state tensions. The Karnataka government blames dairies in Maharashtra and Tamil Nadu for offering higher prices to farmers within Karnataka, while the Tamil Nadu government is blaming private companies from Andhra Pradesh!Funny, the kinds of things that happen when the government enters and obstructs a control system called “prices”.Even as this satire unfolds, the root cause of the milk shortages isn't even being talked about. The Bangalore Milk Union president admitted that “many small milk producers have given up on rearing cows as it has become unsustainable”. Though he doesn't mention the underlying reason for this change, the bans on cow slaughter and recent attacks on people transporting cattle surely have reduced the incentives for farmers from stepping into this minefield called milk production. HomeWorkReading and listening recommendations on public policy matters* [Newsletter] Economic Forces is a must-read newsletter for all public policy enthusiasts.* [Paper] This paper on the effect of a landmark policyWTF called the Freight Equalisation Scheme explains how good intentions can sometimes produce terrible policies. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit publicpolicy.substack.com

In this episode, we talk about "The Five Challenges to Building an Isomorphic Javascript Library" by Nick Fahrenkrog. If the word "isomorphic" scares you this is a must-listen because we do a sort-of decent job explaining it. Joe corrects himself on a V8 Isolates comment from last episode (Cloudflare article here) then proceeds to talk wayyy more about them. Evan babbles about nutrition stuff and is skeptical about VILPA. Oh, and Joe's audio isn't great. Happy New Year!

Jason Chats with Jonathan Chaffer

AI research wunderkind, DeepMind, has long been all fun and games. The London-based organization, owned by Google parent company Alphabet, has used deep learning to train algorithms that can take down world champions at the ancient game of Go and top players of the popular strategy video game Starcraft. Then last year, things got serious when DeepMind trounced the competition at a protein folding contest. Predicting the structure of proteins, the complex molecules underpinning all biology, is notoriously difficult. But DeepMind's AlphaFold2 made a quantum leap in capability, producing results that matched experimental data down to a resolution of a few atoms. In July, the company published a paper describing AlphaFold2, open-sourced the code, and dropped a library of 350,000 protein structures with a promise to add 100 million more. This week, Alphabet announced it will build on DeepMind's AlphaFold2 breakthrough by creating a new company, Isomorphic Labs, in an effort to apply AI to drug discovery. “We are at an exciting moment in history now where these techniques and methods are becoming powerful and sophisticated enough to be applied to real-world problems including scientific discovery itself,” wrote Demis Hassabis, DeepMind founder and CEO, in a post announcing the company. “Now the time is right to push this forward at pace, and with the dedicated focus and resources that Isomorphic Labs will bring.” Hassabis is Isomorphic's founder and will serve as its CEO while the fledgling company gets its feet, setting the agenda and culture, building a team, and connecting the effort to DeepMind. The two companies will collaborate, but be largely independent. “You can think of [Isomorphic] as a sort of sister company to DeepMind,” Hassabis told Stat. “The idea is to really forge ahead with the potential for computational AI methods to reimagine the whole drug discovery process.” While AlphaFold2's success sparked the effort, protein folding is only one step—arguably simpler than others—in the arduous drug discovery process. Hassabis is thinking bigger. Though details are scarce, it appears the new company will build a line of AI models to ease key choke points in the process. Instead of identifying and developing drugs themselves, they'll sell a platform of models as a service to pharmaceutical companies. Hassabis told Stat these might tackle how proteins interact, the design of small molecules, how well molecules bind, and the prediction of toxicity. That the work will be separated from DeepMind itself is interesting. The company's not insignificant costs have largely been dedicated to pure research. DeepMind turned its first profit in 2020, but its customers are mostly Alphabet companies. Some have wondered if it'd face more pressure to focus on commercial products. The decision to create a separate enterprise based on DeepMind research seems to indicate that's not yet the case. If it can keep pushing the field ahead as a whole, perhaps it makes sense to fund a new organization—or organizations, seeded by future breakthroughs—as opposed to diverting resources from DeepMind's more foundational research. Isomorphic Labs has plenty of company in its drug discovery efforts. In 2020, AI in cancer, molecular, and drug discovery received the most private investment in the field, attracting over $13.8 billion, more than quadruple 2019's total. There have been three AI drug discovery IPOs in the last year, and mature startups—including Exscientia, Insilico Medicine, Insitro, Atomwise, and Valo Health—have earned hundreds of millions in funding. Companies like Genentech, Pfizer, and Merck are likewise working to embed AI in their processes. To a degree, Isomorphic will be building its business from the ground up. AlphaFold2 is without a doubt a big deal, but protein modeling is the tip of the drug discovery iceberg. Also, while AlphaFold2 had the benefit of access to hundreds of thousands of freely available, already modeled protein s...

Alphabet announces a new company, Isomorphic Laboratories, that will use AI methods for drug discovery, Meta is reportedly considering opening retail stores to highlight VR products, and DJI announces the Mavic 3 drone. MP3 Please SUBSCRIBE HERE. You can get an ad-free feed of Daily Tech Headlines for $3 a month here. A special thanksContinue reading "Alphabet’s Isomorphic Laboratories To Use AI For Drug Discovery – DTH"

Institutions and isomorphic pressures shaping strategic options by Professor Mat Hughes

Isomorphic means the same but different. So how does being isomorphic in our relationships play out? Join us today as we unpack this idea.

Isomorphic is an adjective that means having a similar form. The Greek prefix I-S-O means ‘equal’ or ‘identical,’ while morphe (MORE fey) is Greek for shape. The two chemicals were isomorphic and yet, despite their similarities, they had very different effects on the body.

This newsletter is really a public policy thought-letter. While excellent newsletters on specific themes within public policy already exist, this thought-letter is about frameworks, mental models, and key ideas that will hopefully help you think about any public policy problem in imaginative ways. It seeks to answer just one question: how do I think about a particular public policy problem/solution?PS: If you enjoy listening instead of reading, we have this edition available as an audio narration on all podcasting platforms courtesy the good folks at Ad-Auris. If you have any feedback, please send it to us.India Policy Watch #1: Sedition, Blasphemy, DefamationInsights on burning policy issues in India- Pranay KotasthaneA Delhi Court Session Judge’s admirable order granting bail to activist Disha Ravi in the #ToolKit case made me reflect on sedition as a concept. Here are a few initial thoughts emanating from that exercise. Fair warning: this is a conceptual discussion and not a legal one. If detailed legal critique interests you, head over to these two articles by Gautam Bhatia (1 & 2). The “crimes” of sedition, blasphemy, and defamation lie along a continuum. They are categorically similar in that they punish the written or spoken word directed at some other entity. Where they differ is the targeted object. Defamation laws punish verbal or written attacks against a person or a group of people. Blasphemy laws punish utterances against something considered sacred by a group of people whereas sedition laws punish utterances that can threaten the State. A Few DefinitionsBefore wading in any further, understanding three political science terms — nation, state, and government — is important. State is a political construct, an abstract political institution. Max Weber’s instrumental definition of the State as “a human community that (successfully) claims the monopoly of the legitimate use of physical force within a given territory” is especially relevant here. To ensure that all its individuals’ liberties are protected, a State is invested with the powers to use violence or force to prevent other belligerent groups from terrorising individuals. It is for this reason that a State maintains armed institutions like the police and the army. Going by this definition, an anti-State act would be the one that challenges the State's monopoly over the legitimate use of physical force. In other words, an act of violence or the use of force by anyone other than the State becomes anti-State. Government is a temporary governing body of the State. If the State is like a corporation, the government is like its management. State is semi-permanent. It will live on until it is overthrown or replaced and a new social contract is established. Unlike the State, the government is composed of a set of people organised into a hierarchy. When the electorate vote, they choose their government and not the State. By this definition, an anti-government act would be the one that criticises the policies, strategies, and directives of the governing body in power.Nation, on the other hand, is a mental construct. Ernest Gellner defines this concept precisely yet comprehensively thus:“Two men are of the same nation if and only if they recognize each other as belonging to the same nation. In other words, nations maketh man; nations are the artefacts of men's convictions and loyalties and solidarities. A mere category of persons (say, occupants of a given territory, or speakers of a given language, for example) becomes a nation if and when the members of the category firmly recognize certain mutual rights and duties to each other in virtue of their shared membership of it. It is their recognition of each other as fellows of this kind which turns them into a nation, and not the other shared attributes, whatever they might be, which separate that category from non-members.”In other words, nations are imagined. People belong to the same nation only if they consider themselves to be so. An anti-national act thus could be of two types. One that denies the existence of such an imagined community. For example, libertarians could argue that only individuals matter and not the groups these individuals are a part of. And the other view imagining a nation along lines different from the dominant belief. For example, communism sees workers across the world as one “nation”.What is Sedition then?With these key differences out of the way, we are now in a position to understand sedition and blasphemy laws. Sedition laws can lie on a continuum. In dictatorships and party-states, sedition laws are applied wantonly to criticisms of the government. That is, being anti-government itself is being seditious. In most modern democracies, however, sedition laws punish only those anti-State actions which have the capability to directly challenge the State’s authority. Thus, criticism of the Republic of India would not count as sedition but inciting violence against the police would count as sedition. Crucially, being anti-national is not the same as being seditious. On the other hand, blasphemy laws penalise a subset of anti-national actions, the ones that call into question something held sacred. As the idea of individual freedom has gained prominence, blasphemy laws have been repealed in many places. Not in India though.The Indian Sedition LawNow we are in a position to understand sedition in India. India’s sedition law i.e. Section 124A of the Indian Penal Code has colonial origins. Unsurprisingly then, being anti-government was reason enough to be labelled seditious. Tilak, Gandhi and scores of other leaders were tried for sedition.After independence, the stated aim was to get rid of sedition laws altogether. That never happened. Sedition law continued in its colonial avatar. What did happen is that the application of such laws reverted to a stricter interpretation. Anti-State acts were penalised and not anti-government ones as a result of a right to freedom of speech and expression. In subsequent court rulings, the scope of sedition was further truncated. Only those anti-State acts that had the tendency to incite violence or disturb law and order were deemed to be seditious. This dissonance between the original definition and application continues to this day. See for yourself. The sedition law says: “Whoever,   by   words,   either   spoken   or written, or by signs, or by visible representation, or otherwise, brings or attempts to bring into hatred or contempt, or excites or attempts to excite disaffection towards, the Government established by law in India, shall be punished with imprisonment for life, to which fine may be added, or with imprisonment which may extend to three years, to which fine may be added, or with fine.Explanation 1.-- The expression "disaffection" includes disloyalty and all feelings of enmity.Explanation 2.--Comments expressing disapprobation of the measures of the Government with a view to obtain their alteration by lawful means, without exciting or attempting to excite hatred, contempt or disaffection, do not constitute an offence under this section.Explanation 3.--Comments expressing disapprobation of the administrative or other action of the Government without exciting or attempting to excite hatred, contempt or disaffection, do not constitute an offence under this section.Note how wide-ranging this law is. Even disloyalty and all feelings of enmity count as sedition. Now read the qualifier that the Supreme Court added in Kedar Nath vs State of Bihar 1962.“..the sections aim at rendering penal only such activities as would be intended, or have a tendency, to create disorder or disturbance of public peace by resort to violence. As already pointed out, the explanations appended to the main body of the section make it clear that criticism of public measures or comment on Government action, however strongly worded, would be within reasonable limits and would be consistent with the fundamental right of freedom of speech and expression. It is only when the words, written or spoken, etc. which have the pernicious tendency or intention of creating public disorder or disturbance of law and order that the law steps in to prevent such activities in the interest of public order.”In non-legalese, for an action to count as seditious, its connection with violence is necessary according to the Supreme Court but not so according to the original framing in the penal code. This dissonance is a problem. To such an extent that the same judge presiding in two similar cases (Disha Ravi’s and Safoora Zargar’s), referring to the same 1962 judgment, reached two diametrically opposite conclusions! In Safoora Zargar’s case, bail was denied on the grounds that the connection of an act with violence is not necessary. In the Disha Ravi case, bail was granted on the grounds that the connection of an act with violence is necessary. The other problem is the political economy of India’s sedition law. Because it is construed as a grave anti-State offence, it is cognisable i.e. investigation and arrest can happen based on just an FIR, and non-bailable i.e. bail is subject to the decision of a sessions judge. Such strict provisions mean that the police slap sedition charges indiscriminately and by the time charges are cleared, many years pass by. The process becomes the punishment.Clearly, this needs fixing. The Way ForwardBroadly, there are three ways out. The first method would be to revise the sedition law to end the dissonance between the text and its subsequent interpretation. Make the link with violence a necessary condition for the application of sedition. A second way is to scrap the law altogether. If the tendency to cause violence is what triggers sedition, there are enough and more laws in place to address such actions. Even if this law were to be struck down, provisions to punish acts inciting violence against State, government, or other people will still be applicable.A third way out is to address the political economy question by making sedition a bailable and non-cognisable offence. With nothing to gain by slapping the additional charge of sedition, its usage is likely to decline. A solution with a similar effect is to make police personnel comply with additional requirements before arresting a person for sedition. The Bombay High Court tried to do this in the Asim Trivedi case by issuing guidelines to police personnel listing specific preconditions. A failure to adhere to these guidelines made the police officer liable to dereliction of duty. To what extent these guidelines been adopted since then, I do not know. Given my biases, the second solution is the ideal one. But it’s also the most unlikely one in the current situation. We in fact run a real risk of going the other way — sedition laws might well revert to punishing anti-government utterances and blasphemy laws might be used more frequently. Given this reality, focusing on changing the incentives of police might be more practical.For now, I’ll leave with these lines in Disha Ravi’s bail order that need to reach far and wide:“Citizens are conscience keepers of government in any democratic Nation. They cannot be put behind the bars simply because they choose to disagreewith the State policies. The offence of sedition cannot be invoked tominister to the wounded vanity of the governments. Difference of opinion,disagreement, divergence, dissent, or for that matter, even disapprobation, are recognised legitimate tools to infuse objectivity in state policies. An aware and assertive citizenry, in contradistinction with an indifferent or docile citizenry, is indisputably a sign of a healthy and vibrant democracy.”India Policy Watch #2: The Coming InflationInsights on burning policy issues in India- RSJLast week Pranay wrote about the Domar rule and how to think about public debt sustainability. Pranay and I have long held economic growth is a moral imperative for India now. Domar’s paper, like Pranay wrote, makes it clear that growth is necessary even if you favour a big government. The argument is simple. Governments are free to borrow and spend on their favoured programmes. They can run deficits without worrying about today’s deficits turning into tomorrow’s higher taxes or higher inflation only if the national income (r) grows at a rate faster than the interest rate (i). That is if “r” > “i”, we are fine with deficit spending. The logic is simple. If you grow faster than the interest rate, you can keep your debt to GDP ratio at a constant level. So, please go ahead and spendbut choose wisely. Spend in areas that will yield higher growth rates in future. Growth will take care of your debt burden.Since we are in the territory of public debt sustainability and role of government spends, I thought it would be useful to bring the Fiscal Theory of the Price Level (FTPL from here on) into this discussion. So, consider this an addendum to Pranay’s piece. Price stability or inflation control is a key goal for all governments in a democracy. Why? Because they want to win elections and nothing irks public than price rise. So, there are two questions in public policy on this issue - a) how do we tame inflation and b) is there an optimal level of controlling it?Now, the usual macroeconomic explanation offered to the first question was simple. Inflation is managed by the monetary policy of the central bank. An independent central bank focused on price stability will manage it by controlling the supply of money. If the total output grows at x per year and the money supply grows at y, then over a period of time the prices will grow at (y-x) per year. That’s your inflation rate. Simple. There’s a problem though. It assumes the demand for money among people today is uniform across. This isn’t true. Because all of us have different beliefs about the future. If our view of future inflation is different, our need to hold money today will be different. This means there could be many paths to price stability other than just the monetary approach. These paths are varied depending on households’ views about the economy’s future state. And that’s influenced by fiscal policy. So, according to FTPL, a tough and independent central bank is good to have but it alone cannot guarantee price stability. Fiscal policy will have to work in tandem. Government’s choice of how it finances its debt has a key role in how inflation plays out in future. The central banker must continue to convince the government to adopt the right stance on fiscal policy.On the second question - how much inflation control is optimal - FTPL suggests allowing price levels to swing to any wild variations to the government’s budget. This gets a bit complicated but a simple summary is that in times of economic shocks like a pandemic it is efficient to allow prices to go up. That done, let me move to add my nuance to Pranay’s explanation of Domar’s rule. No one can argue about “r” > “i” logic. The key questions about the deficit, however, are for how long and how much? If you have a fiscal deficit of one per cent for one year and you take the next five to grow higher than the interest rate to offset it, you’re fine. But what if you keep adding a five or six per cent deficit every year for a decade and more? As a somewhat laidback, retiring fiscal hawk, this is what worries me when I see unlimited deficit spending all around. A trillion here in stimulus and another trillion there and soon we are talking about some real money here. My worry is we have reached a stage where “r” > “i” cannot support the deficit spending. So inflation will come in. That’s my view. A high inflation future is inevitable. Addendum squaredRSJ makes an important point. “r” > “i” is a necessary but insufficient condition. The reality is that “r” needs to be sufficiently greater than “i”. That’s because the “r” > “i” condition rests on the assumption that the primary deficit is zero i.e. the government is only borrowing to pay interest on debts accumulated in the past. That’s not the case in India. The primary deficit in 2019-20 was 1.6 per cent of GDP while it is estimated to be 3.1 per cent in the next financial year. This means a lot of borrowing is being deployed not just for capital investment but also for the day to day running of the government. With higher primary deficits comes higher responsibility to restart economic growth. Not(PolicyWTF): Delhi Government’s Singapore AmbitionsThis section looks at egregious public policies. Policies that make you go: WTF, Did that really happen?— Pranay KotasthaneGiven how we keep going on and on about the urgency of economic growth, this line in the Delhi government’s budget came as a pleasant surprise:“Our goal is that the per capita income of Delhi by the year 2047 is equal to the income of a Singapore citizen. To make this possible, we have to increase the income of our citizens by about 16 times which is a difficult target, but not impossible.”It’s not new for Indian governments to aspire to be like someplace else. Isomorphic mimicry is in fact quite common. Vilas Rao Deshmukh wanted to transform Mumbai into Shanghai more than a decade ago. What’s different this time is the Delhi government has set itself a measurable output target with a defined end date, something most governments refuse to commit to. The Delhi Finance Minister even had a well-thought-out response to the question “Why Singapore?”. He said:“Singapore has one of the most stable economies in the world, with high government revenue and a consistently positive surplus. As a result of its strategic geographical positioning in Asia, the socio-economic context of Singapore is relatable to that of India. In addition to this, Singapore is also a city state which has achieved substantial growth in the past 25 years. So, when we think of Delhi 25 years from now, we envision a Delhi which can stand at par with one of the fastest growing and developed economies in the world.”Setting a clear, measurable income target against which performance can be measured is a welcome change. Hopefully, the other governments are watching. HomeWorkReading and listening recommendations on public policy matters[Article] John Cochrane on fiscal roots of inflation. A great paper.[Article] ‘Disaffection’ and the Law: The Chilling Effect of Sedition Laws in India by Siddharth Narrain is a good overview of the history of sedition in India.[Podcast] Pranay and Saurabh discuss the impossibility theorem of affirmative action on Puliyabaazi. Get on the email list at publicpolicy.substack.com

Wir möchten euch auf unserem Weg zu zwei neuen Webseiten mitnehmen und beginnen in dieser Folge mit der Vorstellung des High-Level-Frameworks Nuxt.js für Vue.js-Apps. Unser Ziel ist die Generalüberholung der Webseiten der programmier.bar und unseres Entwicklerstudios Lotum. In dieser Folge erläutern wir grundlegende Begriffe wie Single Page Application (SPA), Isomorphic und Universal Web Apps, Server Side Rendering (SSR) und Static Site Generation. Nuxt.js ist ein sogenanntes Opinionated Framework, das den Rahmen in der Entwicklung stark vorgibt und von Beginn an bis zur fertigen Seite unterstützt. Damit wird der Werkzeugkasten optionaler Module einfacher bedienbar und die moderne, weltweit erreichbare und vor allem schnelle Webseite ist nicht mehr weit. Picks of the Day Dennis: Die iOS 14 Public Beta ist erstaunlich stabil und eine Empfehlung wert. Achtung Edit: Die Corona-Warn-App funktioniert nicht mehr mit iOS 14! Sebi: Entwickler-Tools der Developer Preview von Safari Fabi: Dedicated Devtools für Node im Chrome Inspect Tab (chrome://inspect) Jojo: CodePen-Playground unterstützt jetzt auch Flutter Schreibt uns! Schickt uns eure Themenwünsche und euer Feedback. podcast@programmier.bar Folgt uns! Bleibt auf dem Laufenden über zukünftige Folgen und virtuelle Meetups und beteiligt euch an Community-Diskussionen. Twitter Instagram Facebook Meetup YouTube Musik: Hanimo

Pranay Kotasthane heads research at the Takshashila Institution. Pranay started his career as a policy analyst focusing on geopolitics at the Takshashila Institution in March 2014. His research interests focus on geostrategy, geopolitics of the Indian subcontinent, and public economics. Pranay is currently working on the New World Order project, the Intelligence Reform project, and State Finances in India. He also tracks India's foreign policy equations with Afghanistan and Pakistan. 1.Pranay's journey 2. What is economic nationalism? 3.Bipin Chandra. Economic Nationalism 1880 to 1905 4. What is different about Economic Nationalism? 5. Where we have seen economic nationalism recently? 6.Smoot-Hawley Tariff Act 7.https://en.wikipedia.org/wiki/Smoot%E2%80%93Hawley_Tariff_Act 8.Economic Nationalism in the Indian Context 9.Importance of Free trade 10.Types of economic nationalism 11.What if One Rupee is equivalent to One Dollar? 12. What is Autarky? 13. Why can't we change our exchange rates now? 14.Reservations for small sector industries 15. Do we see an economic right party in the mainstream? 16.The mainstream idea around India China economic policies 17. How feasible is it to restrict China? 18. Decoding the objectives to restrict China. The famous Sonam Wangchuk video. 19.Trade Deficit 20.Comparative advantage and Opportunity cost of Chinese production 21.The comparative advantage of India 22.Levers of growth for India 23.Import tariffs and its implications 24.Risks of investors 25.Investment restrictions from China 26.Isomorphic mimicry 27.Instruments against China 28. How do Chinese investors perceive these hyper-nationalistic campaigns? 29.Belt and Road initiative 30. How feasible is it to become indigenous? 31.R&D investments of India 32.Questions from listeners 33. Is China being's expansionist? - Japnit 34. Why we don't play our Tibet card? – Soumya 35. How will the world change if Chiba becomes a global power? Maaz 36. In what ways can China's progress be useful to India and in what ways can it be cannibalizing? – Priya 1. प्रणय की यात्रा 2. आर्थिक राष्ट्रवाद क्या है? 3. बिपिन चंद्र। आर्थिक राष्ट्रवाद 1880 से 1905 तक 4. आर्थिक राष्ट्रवाद के बारे में क्या अलग है? 5. हाल ही में हमने आर्थिक राष्ट्रवाद कहाँ देखा है? 6. स्मूट-हॉले टैरिफ एक्ट 7. https://en.wikipedia.org/wiki/Smoot%E2%80%93Hawley_Tariff_Act 8. भारतीय संदर्भ में आर्थिक राष्ट्रवाद 9. मुक्त व्यापार का महत्व 10. आर्थिक राष्ट्रवाद के प्रकार 11. क्या होगा यदि एक रुपया एक डॉलर के बराबर है? 12. आटार्की क्या है? 13. अब हम अपनी विनिमय दरें क्यों नहीं बदल सकते? 14. छोटे क्षेत्र के उद्योगों के लिए आरक्षण 15. क्या हम एक आर्थिक अधिकार पार्टी को मुख्यधारा में देखते हैं? 16. भारत चीन आर्थिक नीतियों के आसपास मुख्यधारा का विचार 17. चीन को प्रतिबंधित करना कितना संभव है? 18. चीन को प्रतिबंधित करने के उद्देश्यों को डिकोड करना। प्रसिद्ध सोनम वांगचुक वीडियो। 19. व्यापार में कमी 20. चीनी उत्पादन का तुलनात्मक लाभ और अवसर लागत 21. भारत का तुलनात्मक लाभ 22. भारत के लिए विकास की लीवर 23. आयात शुल्क और इसके निहितार्थ 24. निवेशकों के जोखिम 25. चीन से निवेश प्रतिबंध 26. आइसोमॉर्फिक मिमिक्री 27. चीन के खिलाफ उपकरण 28. चीनी निवेशक इन अति-राष्ट्रवादी अभियानों को कैसे देखते हैं? 29. बेल्ट एंड रोड पहल 30. स्वदेशी बनना कितना संभव है? 31. भारत का R & D निवेश 32. श्रोताओं से प्रशन 33. क्या चीन का विस्तारवादी है? - जापनीत 34. हम अपना तिब्बत कार्ड क्यों नहीं खेलते हैं? - सौम्या 35. अगर चिबा वैश्विक शक्ति बन जाए तो दुनिया कैसे बदल जाएगी? माज 36. किन तरीकों से चीन की प्रगति भारत के लिए उपयोगी हो सकती है और किन तरीकों से यह नरभक्षण हो सकता है? - प्रिया

Добрый день уважаемые слушатели. Представляем новый выпуск подкаста RWpod. В этом выпуске: Ruby Ruby 2.7 introduces numbered parameters as default block parameters Rails adds jitter to ActiveJob::Exceptions.retry_on RubyKaigi 2020 announcements on the Novel Coronavirus COVID-19 outbreak Hanami::API on Amazon AWS Lambda Writing a Ruby Gem Specification Optimizing full-text search with Postgres materialized view in Rails Converting Unix epoch timestamps to Ruby objects Chaskiq - a 100% open source conversational marketing platform build as an alternative for Intercom, Drift, and others FakeRedis - a fake implementation of redis-rb for machines without Redis or test environments Syntax Highlighting with Action Text Web Rollup 2.0 Released Isomorphic-git version 1.0 An Interactive Introduction to D3 The Node.js best practices list 7 Types of Native Errors in JavaScript You Should Know The JavaScript Beginner’s Handbook (2020 Edition) Awesome Demos Roundup #14 Inspirational Websites Roundup #13 Stryker - test your tests with mutation testing Vue Formulate - the easiest way to build forms with Vue Ls-lint - an extremely fast file and directory name linter

Welcome to Farming Eternal the only Eternal draft podcast for farmers. We have another great episode. Hard to top last weeks interview with Isomorphic but we did our best. In this weeks episode we talk card of the week, thank everyone for sending in decklists, give a few tips to get better at draft and review a draft from yoursoulmate. Finally we talk some FJS and FTP. Here is a link to Yoursoulmates draft https://imgur.com/gallery/zZYyRJe Thank you all for listening. And as a reminder if you have any 7 win drafts please send your decklist to farmingeternal@gmail.com. You can access our spreadsheet here. Lots of great decks and stats to be found. https://docs.google.com/spreadsheets/d/1lAJlF4sinN00CN-vL3MQB0x9iw8G7XKzp3pZL5CS_UY/edit#gid=144815197 We also accept feedback and drafts to review.

It's been 2 weeks. We recorded last week but the episode disappeared. But fear not we are still here. This week we review some sweet 7 win drafts, "talk" with Isomorphic, and review a draft by our friend Ben, who can be found whispering on twitch at https://www.twitch.tv/bengrasher Here is his list with 1 cut to go https://drive.google.com/open?id=1LUg5os4CJFMpAAB3aR0WlZIAcuVK_Ioo Also potential Gold drops stream on 3/13 from 6:30-9:30 EST. Stay tuned for more details. Finally, please send any 7 win decklists to farmingeternal@gmail.com and you can find our spreadsheet here: https://docs.google.com/spreadsheets/d/1lAJlF4sinN00CN-vL3MQB0x9iw8G7XKzp3pZL5CS_UY/edit#gid=144815197 Thanks for listening

On the verge of his 50th birthday, Chris’s former colleague Ken Ibrahim looks back at an incredible career in which his childhood dreams came spectacularly true. Ken’s interest in visual effects began at the age of nine, when he and his brother were inspired by Star Wars and Star Trek to create Super 8 films, complete with hand-drawn visual effects. He was introduced to computers at high school, and shortly afterwards he made the leap to Japan where he ended up as a programmer – and occasional voice artist – at SEGA. Then Ken returned to the US to work at companies such as PDI, Cinesite, Square and Digital Domain on movies like Shrek, Final Fantasy: The Spirits Within, X-Men 2 and 2012. He landed in nerd heaven, and met some of the universe’s heroes, when he joined JJ Abrams’ Bad Robot studio, to work on the franchises which inspired his career. Ken’s an entertaining podcast guest, and he and Chris discuss everything from digital humans to Isomorphic web design. You’ll also find out how he enjoys free beer, ball games and concerts in San Francisco.

Добрый день уважаемые слушатели. Представляем новый выпуск подкаста RWpod. В этом выпуске: Ruby Rails 5.2 sets Ruby version in Gemfile and adds .ruby-version file by default, Increase reliability of background job processing using super_fetch of Sidekiq Pro и 4 Reasons Why I Think Google Cloud Will Take Over Cloud Computing Space Rails Testing Antipatterns: Models, Email with Amazon SES from Rails on EC2 и TensorStream - a reimplementation of TensorFlow for ruby JavaScript Real-time Human Pose Estimation in the Browser with TensorFlow.js, Optimizing React: Virtual DOM explained и Introducing Guess.js - a toolkit for enabling data-driven user-experiences on the Web Isomorphic-git - a pure JavaScript implementation of git for node and browsers, ScrollHint - a JS library to suggest that the elements are scrollable horizontally, with the pointer icon и GraphQL Full Course - Novice to Expert

In the latest episode of JAMstack Radio, Brian speaks with Phil Hawksworth, Technical Director at R/GA and Eli Williamson, Creative Director at Netlify about Isomorphic rendering in the JAMstack. The post Ep. #8, Isomorphic Rendering in the JAMstack appeared first on Heavybit.

In the latest episode of JAMstack Radio, Brian speaks with Phil Hawksworth, Technical Director at R/GA and Eli Williamson, Creative Director at Netlify about Isomorphic rendering in the JAMstack.

1:00 Intro to guests Brian Douglas and Matt Christensen 2:20 Definition of JAMStack 8:12 JAMStack and confusion over nomenclature 12:56 JAMStack and security, reliability and performance 17:05 Example of traffic spike for company Sphero 18:26 Meaning of hyperdynamic 20:35 Future and limits of JAMStack technology 26:01 Controlling data and APIs versus using third parties 28:10 Netlify.com and JAMStack 31:16 APIs, JavaScript framework and libraries recommended to start building on JAMStack 35:13 Resources and examples of JAMStack: netlify.com, Netlify blog, JAMStack radio, JAMStack SF Meetup QUOTES: “I think in the next couple of years we’re going to see the limits being pushed a lot for what you can do with this.” - Matt “Today we’re starting to see really interesting, really large projects getting built with this approach.” - Matt “If you can farm 100% of your backend off to third parties, I feel like that really limits a lot of the interesting things you can do as a developer.” - Brian PICKS: Early History of Smalltalk (Jamison) React Rally 2016 videos (Jamison) FiveStack.computer (Jamison) Falsehoods programmers believe about time (Aimee) Nodevember conference (Aimee) 48 Days Podcast (Charles) Fall of Hades by Richard Paul Evans (Charles) Jon Benjamin Jazz (Brian) RailsConf 2016 (Brian) React Native (Brian) Book of Ye Podcast (Brian) Aurora by Kim Stanley Robinson (Matt) Sequoia Capital website Sphero website Isomorphic rendering on the Jam Stack by Phil Hawksworth SPONSORS: Front End Masters Hired.com

1:00 Intro to guests Brian Douglas and Matt Christensen 2:20 Definition of JAMStack 8:12 JAMStack and confusion over nomenclature 12:56 JAMStack and security, reliability and performance 17:05 Example of traffic spike for company Sphero 18:26 Meaning of hyperdynamic 20:35 Future and limits of JAMStack technology 26:01 Controlling data and APIs versus using third parties 28:10 Netlify.com and JAMStack 31:16 APIs, JavaScript framework and libraries recommended to start building on JAMStack 35:13 Resources and examples of JAMStack: netlify.com, Netlify blog, JAMStack radio, JAMStack SF Meetup QUOTES: “I think in the next couple of years we’re going to see the limits being pushed a lot for what you can do with this.” - Matt “Today we’re starting to see really interesting, really large projects getting built with this approach.” - Matt “If you can farm 100% of your backend off to third parties, I feel like that really limits a lot of the interesting things you can do as a developer.” - Brian PICKS: Early History of Smalltalk (Jamison) React Rally 2016 videos (Jamison) FiveStack.computer (Jamison) Falsehoods programmers believe about time (Aimee) Nodevember conference (Aimee) 48 Days Podcast (Charles) Fall of Hades by Richard Paul Evans (Charles) Jon Benjamin Jazz (Brian) RailsConf 2016 (Brian) React Native (Brian) Book of Ye Podcast (Brian) Aurora by Kim Stanley Robinson (Matt) Sequoia Capital website Sphero website Isomorphic rendering on the Jam Stack by Phil Hawksworth SPONSORS: Front End Masters Hired.com

1:00 Intro to guests Brian Douglas and Matt Christensen 2:20 Definition of JAMStack 8:12 JAMStack and confusion over nomenclature 12:56 JAMStack and security, reliability and performance 17:05 Example of traffic spike for company Sphero 18:26 Meaning of hyperdynamic 20:35 Future and limits of JAMStack technology 26:01 Controlling data and APIs versus using third parties 28:10 Netlify.com and JAMStack 31:16 APIs, JavaScript framework and libraries recommended to start building on JAMStack 35:13 Resources and examples of JAMStack: netlify.com, Netlify blog, JAMStack radio, JAMStack SF Meetup QUOTES: “I think in the next couple of years we’re going to see the limits being pushed a lot for what you can do with this.” - Matt “Today we’re starting to see really interesting, really large projects getting built with this approach.” - Matt “If you can farm 100% of your backend off to third parties, I feel like that really limits a lot of the interesting things you can do as a developer.” - Brian PICKS: Early History of Smalltalk (Jamison) React Rally 2016 videos (Jamison) FiveStack.computer (Jamison) Falsehoods programmers believe about time (Aimee) Nodevember conference (Aimee) 48 Days Podcast (Charles) Fall of Hades by Richard Paul Evans (Charles) Jon Benjamin Jazz (Brian) RailsConf 2016 (Brian) React Native (Brian) Book of Ye Podcast (Brian) Aurora by Kim Stanley Robinson (Matt) Sequoia Capital website Sphero website Isomorphic rendering on the Jam Stack by Phil Hawksworth SPONSORS: Front End Masters Hired.com

Sign up for Angular Remote Conf!   02:35 - Jeff Whelpley Introduction Twitter Blog GetHuman Angular Air 02:53 - Patrick Stapleton Introduction Twitter GitHhub Blog Angular Class 03:39 - Advantages of Server Rendering 14:28 - Universal & Isomorphic 24:11 - Caching and Load Balancing Rendering the Application Rendering the Application with Data 41:29 - Service Worker 43:02 - Bindings 46:36 - Rendering Angular 49:00 - Prerendering 52:41 - Rendering in Angular 2 58:38 - Time Table Picks 14 by Peter Clines (Lukas) ZPacks Cuben Fiber Arc Backpacks (Ward) Angular Remote Conf (Chuck) Iron Sharpens Iron (Chuck) View from the Top (Chuck) GetHuman (Jeff) Angular Universal (Jeff) Open Source (Patrick) Angular Summit (Patrick) AngularConnect (Patrick)

Sign up for Angular Remote Conf!   02:35 - Jeff Whelpley Introduction Twitter Blog GetHuman Angular Air 02:53 - Patrick Stapleton Introduction Twitter GitHhub Blog Angular Class 03:39 - Advantages of Server Rendering 14:28 - Universal & Isomorphic 24:11 - Caching and Load Balancing Rendering the Application Rendering the Application with Data 41:29 - Service Worker 43:02 - Bindings 46:36 - Rendering Angular 49:00 - Prerendering 52:41 - Rendering in Angular 2 58:38 - Time Table Picks 14 by Peter Clines (Lukas) ZPacks Cuben Fiber Arc Backpacks (Ward) Angular Remote Conf (Chuck) Iron Sharpens Iron (Chuck) View from the Top (Chuck) GetHuman (Jeff) Angular Universal (Jeff) Open Source (Patrick) Angular Summit (Patrick) AngularConnect (Patrick)

Sign up for Angular Remote Conf!   02:35 - Jeff Whelpley Introduction Twitter Blog GetHuman Angular Air 02:53 - Patrick Stapleton Introduction Twitter GitHhub Blog Angular Class 03:39 - Advantages of Server Rendering 14:28 - Universal & Isomorphic 24:11 - Caching and Load Balancing Rendering the Application Rendering the Application with Data 41:29 - Service Worker 43:02 - Bindings 46:36 - Rendering Angular 49:00 - Prerendering 52:41 - Rendering in Angular 2 58:38 - Time Table Picks 14 by Peter Clines (Lukas) ZPacks Cuben Fiber Arc Backpacks (Ward) Angular Remote Conf (Chuck) Iron Sharpens Iron (Chuck) View from the Top (Chuck) GetHuman (Jeff) Angular Universal (Jeff) Open Source (Patrick) Angular Summit (Patrick) AngularConnect (Patrick)

Summary In episode 49 Danny Blue (@dee_bloo) has a one-on-one talk with Web Application Master & JavaScript Guru Eric Elliott (@_ericelliott).  Danny & Eric cover several exciting development topics including event based development, functional programming, Web Assembly, teaching JavaScript, helping to stop homelessness with code, & more. Resources Learn JavaScript with Eric Elliott - https://ericelliottjs.com/ Eric on Web Assembly - https://medium.com/javascript-scene/what-is-webassembly-the-dawn-of-a-new-era-61256ec5a8f6 StampIt 2.0 - https://github.com/stampit-org/stampit/releases/tag/v2.0.3 Campaign to fight Homelessness - Kickstarter - https://www.kickstarter.com/projects/ericelliott/learn-javascript Blog - https://medium.com/the-backer-army/fighting-poverty-with-code-d1ed3ebd982d react-stampit - https://github.com/stampit-org/react-stampit nodeschool.io functional programming (on runnable) - http://code.runnable.com/VQuZjvia8Gxcqkpy/nodeschool-io-s-functional-programming-in-javascript-course-available-in-your-browser-for-node-js-and-freecodecamp jsx - https://facebook.github.io/react/docs/jsx-in-depth.html Tim Oxley's Functional Programming workshop - https://github.com/timoxley/functional-javascript-workshop TC-39 - http://ecma-international.org/memento/TC39.htm Jafar Husain - https://twitter.com/jhusain Event Machine - https://github.com/eventmachine/eventmachine Twisted - https://github.com/twisted/twisted Host Danny Blue (@dee_bloo) - Sr. Front End Engineer at Deloitte Digital

Jeff is joined by Michael Jackson and Ryan Florence to discuss what makes the technology and innovations coming from the React.js community really special.

Jeff interviews Spike Brehm, a web engineer at Airbnb, to discuss building web apps which share code, templates, business logic, and the tools which help enable this today.