Works in Progress Podcast

A hundred years ago, insulin was scraped from pig pancreases. Today, it’s made by bacteria in giant tanks. In the second part of a mini series on proteins, drug development and AI, Saloni tells the story of how insulin went from a crude animal extract to the first genetically-engineered drug, kickstarting the biotech industry along the way.Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.Saloni’s substack newsletter: https://www.scientificdiscovery.dev/Jacob’s blog: https://blog.jacobtrefethen.com/ Books:Genentech: The beginnings of biotech by Sally Smith HughesArticles:FDA (2007). Celebrating a Milestone: FDA's Approval of First Genetically-Engineered Product https://fda.report/media/110447/Celebrating-a-Milestone--FDA%27s-Approval-of-the-First-Genetircally-Engineered-Product.pdf Genentech (2016). Cloning Insulin https://www.gene.com/stories/cloning-insulin Arthur Riggs (2020). Making, Cloning, and the Expression of Human Insulin Genes in Bacteria: The Path to Humulin https://academic.oup.com/edrv/article/42/3/374/6042201 Podcasts:Novo Nordisk (Ozempic) by the Acquired podcast https://www.acquired.fm/episodes/novo-nordisk-ozempic Acknowledgements:Aria Babu, editor at Works in ProgressAdrian Bradley, on-site producerAnna Magpie, fact-checkingAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy

Social scientist Alice Evans talks about why, despite a superficially similar feminist movement in East Asia, Western feminism has been much successful. Alice, Sam and Aria talk about dating markets, drinking culture at work, top-down media control, and what tax policy is best for motivating people to have more children.For more of Alice's work, check out her Substack.Go to worksinprogress.co to read more from Works in Progress.ReferencesFlowers of Fire: The Inside Story of South Korea's Feminist Movement and What It Means for Women' s Rights Worldwide Paperback by Hawon JungThe clan and the corporation: Sustaining cooperation in China and Europe by Avner Greif and Guido TabelliniThe Swedish Theory of Love: Individualism and Social Trust in Modern Sweden by Henrik Berggren  and Lars TrägårdhDrunk: How We Sipped, Danced, and Stumbled Our Way to Civilization Hardcover by Edward Slingerland

This episode kicks off a mini-series on proteins, drug development and AI. Saloni and Jacob explore the world of proteins, including how proteins fold into complex shapes, why that complexity matters and how crowded and dynamic the inside of a cell really is; and they exchange surprising statistics about proteins.Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.You can watch or listen on YouTube, Spotify, or Apple Podcasts.Saloni’s substack newsletter: https://www.scientificdiscovery.dev/Jacob’s blog: https://blog.jacobtrefethen.com/ Books:Ron Milo and Rob Phillips. Biology by the numbers https://book.bionumbers.org/ Carl Ivar Branden and John Tooze (1999) Introduction to protein structure https://www.taylorfrancis.com/books/mono/10.1201/9781136969898/introduction-protein-structure-john-tooze-carl-ivar-branden Articles:Niko McCarty (2023). Biology is a burrito. https://www.asimov.press/p/burrito-biology  Rhiannon Morris, Katrina Black, and Elliott Stollar (2022) Uncovering protein function: from classification to complexes. https://pmc.ncbi.nlm.nih.gov/articles/PMC9400073/ Victor Muñoz and Michele Cerminara (2016) When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches https://portlandpress.com/biochemj/article/473/17/2545/49248/When-fast-is-better-protein-folding-fundamentals Image credits:Chang et al. (2012) Egg white in organic electronics. https://spie.org/news/4149-egg-white-in-organic-electronics [diagram of egg white denaturing and cross-linking]John Kendrew’s model of myoglobin’s structure; via Carl Ivar Branden and John Tooze (1999) Introduction to protein structure.Carl Ivar Branden and John Tooze (1999) Introduction to protein structure. [diagram of amino acids and protein structure]Ron Milo and Rob Phillips. Which is bigger, mRNA or the protein it codes for? https://book.bionumbers.org/which-is-bigger-mrna-or-the-protein-it-codes-for/ [diagram of myoglobin mRNA vs protein]Scitable (2014). Microtubules and Filaments. https://www.nature.com/scitable/topicpage/microtubules-and-filaments-14052932/ [diagram of microtubules]

Is it better to be run by engineers, lawyers or regulators? Can you build an economy on luxury handbags or do you need advanced manufacturing? Dan Wang, author of Breakneck: China's Quest to Engineer the Future discusses why China outbuilds America, how the young and ambitious succeed in China, and the secret to finding the best Chinese restaurants.You can order his new book here, read his annual letters on China here, and check out London's best Suzhou noodles here.If you want more from Works in Progress you can read the magazine here or listen to our episode about land in East Asia here.

Why is Chinese housing so expensive despite being oversupplied? How did land reforms in Russia lead to the Bolshevik revolution? What killed Georgism? The Economist’s Wall Street Editor, Mike Bird, discusses the underrated economics of land.You can preorder Mike's book here and read more about land readjustment in Works in Progress Issue 19.

Historian Anton Howes discusses how Henry VIII turned Britain into an economic backwater – making it the unlikeliest place for the Industrial Revolution to happen. But, he explains it only took a small cabal of people who understood the problems of the time to turn the fate of the country (and thus, the world) around.You can learn more about the history of the Industrial Revolution on Anton's Substack, Age of Invention. And you can learn more about progress at Works in Progress. 

Why does London dominate Britain's economy, whereas Germany's is spread out across the whole country? Why don't restaurants scale well? What kind of social science research (if any) should the government be funding? Stian Westlake – Executive Chair of the Economic and Social Research Council and author of Capitalism Without Capital: The Rise of the Intangible Economy – joins the Works in Progress podcast to discuss these questions.

Before the twentieth century, most cities were highly permissive about what people were allowed to build on their land. Nearly all Western householders lost these liberties during the first half of the twentieth century. Samuel Hughes calls this phenomenon The Great Downzoning. In the first episode of the Works in Progress Podcast, he describes how and why this happened, and what it means for modern pro-housing campaigners.

Lenacapavir is a new HIV drug that blocks infections with an efficacy rate of nearly 100%, and it could completely change the fight against HIV worldwide. Saloni and Jacob talk about the development and prospects for this new drug, as well as the history of HIV, the initial discovery of retroviruses, and how HIV was transformed from a death sentence to a manageable condition.Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.00:00 Intro03:52 How was HIV discovered? Where did it come from, and how does it attack the body and cause AIDS?38:10 Antiretrovirals: How did scientists develop breakthrough HIV drugs — from azidothymidine to protease inhibitors to PrEP?1:51:35 How does prevention and treatment work today?2:19:03 HIV’s capsid and the breakthrough of lenacapavir, the first-approved HIV capsid inhibitor2:50:36 How to develop long-lasting treatments3:14:45 Lenacapavir’s near 100% efficacy in clinical trials3:48:40 The impact of global programs against HIV, and can we now end HIV?Saloni’s substack newsletter: https://www.scientificdiscovery.dev/Jacob’s blog: https://blog.jacobtrefethen.com/ Books:How to Survive a Plague — by David France (2016). [Mentioned as a history of the science and activism against the AIDS epidemic, and the protease-inhibitor breakthrough.] https://surviveaplague.com/ And the Band Played On — Randy Shilts (1987). [Mentioned as an account of the early years of AIDS.] https://us.macmillan.com/books/9780312374631/andthebandplayedon/ Drug development stories: From bench to bedside — Elsevier (2024). [Mentioned as containing a history of the development of lenacapavir] https://shop.elsevier.com/books/drug-discovery-stories/yu/978-0-443-23932-8 Retrospectives:The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic — Samuel Broder (2015). https://doi.org/10.1016/j.antiviral.2009.10.002 History of the discoveries of the first human retroviruses: HTLV-1 and HTLV-2 — Robert Gallo (2005). https://doi.org/10.1038/sj.onc.1208980 A Look at Long Acting Drugs — Anne de Bruyn Kops for Open Philanthropy (2025). https://bit.ly/long-acting-drugs-op How To Save Twenty Million Lives, with Dr Mark Dybul — Statecraft (2023)  https://www.statecraft.pub/p/saving-twenty-million-lives The Road to Fortovase. A History of Saquinavir, the First Human Immunodeficiency Virus Protease Inhibitor — Redshaw et al. (2000) https://link.springer.com/chapter/10.1007/978-3-642-57092-6_1 Articles:The origin of genetic diversity in HIV-1 — Smyth et al. (2012). [Mentioned as a review about HIV’s recombination, which described it as “a primitive form of sexual reproduction”] https://www.sciencedirect.com/science/article/pii/S0168170212002122 PF74 Reinforces the HIV-1 Capsid To Impair Reverse Transcription-Induced Uncoating — Rankovic et al. (2018) https://doi.org/10.1128/JVI.00845-18 Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons — Kelley et al. (2024) https://www.nejm.org/doi/full/10.1056/NEJMoa2411858 Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women — Bekker et al. (2024) https://www.nejm.org/doi/10.1056/NEJMoa2407001 The evolution of HIV-1 and the origin of AIDS — Sharp and Hahn (2010) https://doi.org/10.1098/rstb.2010.0031 Pathogenic mechanisms of HIV disease — Moir et al. (2011) https://doi.org/10.1146/annurev-pathol-011110-130254 Estimating per-act HIV transmission risk: a systematic review — Patel et al. (2012) https://journals.lww.com/aidsonline/fulltext/2014/06190/Estimating_per_act_HIV_transmission_risk__a.14.aspx The structural biology of HIV-1: mechanistic and therapeutic insights — Engelman and Cherepanov (2012) https://doi.org/10.1038/nrmicro2747 Challenges and opportunities in the development of complex generic long-acting injectable drug products — O’Brien et al. (2021) https://doi.org/10.1016/j.jconrel.2021.06.017 Making a “Miracle” HIV Medicine — Nahas (2025) https://press.asimov.com/articles/hiv-medicine Highly active antiretroviral therapy transformed the lives of people with HIV — Dattani (2024) https://ourworldindata.org/data-insights/highly-active-antiretroviral-therapy-transformed-the-lives-of-people-with-hiv Videos:Mini-Lecture Series: HIV Capsid Inhibitors: Mechanism of Action — David Spach, National HIV Curriculum (2024) https://www.youtube.com/watch?v=iZ9KDxV5Zbs&ab_channel=NationalHIVCurriculum Image credits:Mini-Lecture Series: HIV Capsid Inhibitors: Mechanism of Action — David Spach, National HIV Curriculum (2024) [Multiple diagrams of HIV capsid and lenacapavir’s effect.]Saloni Dattani; Our World in Data (2024) Highly active antiretroviral therapy transformed the lives of people with HIV. [Graph of decline in HIV/AIDS mortality after HAART was introduced.]Engelman and Cherepanov (2012). The structural biology of HIV-1: mechanistic and therapeutic insights. [Diagram of HIV’s entry into the cell.]Susan Moir, Tae-Wook Chun, Anthony S Fauci (2011). Pathogenic mechanisms of HIV disease. [Diagram of HIV replication rates over time, contrasting acute and chronic infection.]Saloni Dattani, adapted from Patel et al. (2014). Estimating per-act HIV transmission risk: a systematic review. [Bar chart of risks of contracting HIV from different sources when unprotected.]Thomas Splettstoesser under CC-BY. [Diagram of HIV’s internal structure.]Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women — Bekker et al. (2024) [Chart of lenacapavir’s efficacy.]Our World in Data based on Joint United Nations Programme on HIV/AIDS (2024). [Chart of global HIV deaths over time.]Acknowledgements:Douglas Chukwu, researcher at Open PhilanthropySanela Rankovic, Acting Instructor at the In...

Coming soon: the Works in Progress Podcast. Featuring underrated ideas to improve the world – for bigger, more beautiful cities; clean energy that's too cheap to meter; truly pathbreaking scientific research; everyday progress in things like food and drink; and more.Plus: Hard Drugs, a new series hosted by Saloni Dattani and Jacob Trefethen about medical progress and the quest to eradicate the world's worst diseases.Subscribe now.