Works in Progress Podcast – Détails, épisodes et analyse

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.

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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 Intro
03:52 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 inhibitor
2:50:36 How to develop long-lasting treatments
3:14:45 Lenacapavir’s near 100% efficacy in clinical trials
3:48:40 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 
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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 Philanthropy
• Sanela Rankovic, Acting Instructor at the In...

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.

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.