Episodios

  • Should everyone be taking statins?
    Feb 27 2026
    Heart disease is the leading cause of death worldwide, but it’s also one of medicine’s biggest success stories. Since the 1950s, the risk of dying from cardiovascular disease has fallen dramatically, thanks to public health efforts, emergency care, medical innovation, and surgeries.In this episode, Jacob and Saloni explore the cholesterol revolution: from statins discovered in fungi to new drugs that cut LDL cholesterol by 60% and last for months, driven by breakthroughs in genetics, monoclonal antibodies, RNA therapies, and modern medicinal chemistry. They talk about how cholesterol travels through the bloodstream, how it causes atherosclerosis and heart disease, and why it took nearly a century for scientists to form the consensus that lowering cholesterol saves lives.Hard Drugs is a podcast from Works in Progress and Coefficient Giving about medical innovation presented by Saloni Dattani and Jacob Trefethen.You can watch or listen on YouTube, Spotify, or Apple Podcasts.Chapters: 0:00:00 Introduction13:35 The decline in heart disease mortality31:02 Surprising facts about cholesterol55:40 The lipid hypothesis: 7 lines of evidence for the harms of LDL cholesterol1:22:15 How cholesterol works1:30:40 The discovery of statins1:48:44 Should everyone be on statins?1:57:10 PCSK9 drugs and beyond2:22:56 Summary Saloni’s substack newsletter: https://www.scientificdiscovery.dev/Jacob’s blog: https://blog.jacobtrefethen.com/ Acknowledgements:Aria Babu, editor at Works in ProgressGraham Bessellieu, video editorAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Coefficient GivingBooksDaniel Steinberg (2007) The Cholesterol Wars.Jie Jack Li (2009) Triumph of the Heart: The Story of Statins.Blog postsJames Stein (2025) Lipid and lipoprotein basics series. https://jamesstein18.substack.com/p/part-i-lipid-and-lipoprotein-basics ArticlesAkira Endo (2017) Discovery and Development of Statins https://doi.org/10.1177/1934578X1701200801 Joseph L Goldstein, Michael S Brown (2010) History of discovery: The LDL receptor. https://pmc.ncbi.nlm.nih.gov/articles/PMC2740366/ Patty W. Siri-Tarino and Ronald M. Krauss (2016) The early years of lipoprotein research: from discovery to clinical application https://pubmed.ncbi.nlm.nih.gov/27474223/ Eun Ji Kim and Anthony S. Wierzbicki (2020) The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease https://pubmed.ncbi.nlm.nih.gov/32537117/ Patrick W. Siri-Tarino et al. (2010) Saturated fat, carbohydrate, and cardiovascular disease. https://www.pnas.org/doi/10.1073/pnas.94.9.4312Saloni Dattani (2025) Death rates from cardiovascular disease have fallen dramatically — what were the breakthroughs behind this? https://ourworldindata.org/cardiovascular-deaths-declineCholesterol Treatment Trialists’ (CTT) Collaboration (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. https://doi.org/10.1016/S0140-6736(10)61350-5E. J. Mills et al. (2011) Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. https://pubmed.ncbi.nlm.nih.gov/20934984/Julia Brandts and Kausik K. Ray (2023) Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. https://www.nature.com/articles/s41569-023-00860-8 VideosNinja Nerd (2018) Lipoprotein metabolism https://www.youtube.com/watch?v=wQY0xpwqPfQ
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    2 h y 55 m
  • Why Europe has stagnated
    Feb 25 2026

    Europe is now much poorer than America. Is it because Europe doesn’t have a big tech giant? Can we blame the bureaucrats in Brussels? What happened to make Germany ban combustion cars? Should we turn Europe into a playground for American and Asian elites? Are the far right going to solve Europe’s energy problems by burning coal to own the libs? Pieter, Sam and Aria discuss why Europe hasn’t grown very much and what we can do to save it.

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    1 h y 30 m
  • Inflation in Rome, Weimar Germany and Soviet Russia with Mark Koyama
    Feb 11 2026

    People hate inflation. It undermines faith in the government so people obstruct policies that require faith in the state, like nuclear power, and in democracies it drives them to vote for extremist parties. Ben and Pieter sit down with economic historian Mark Koyama and discuss the fallout of historical inflation crises from the Roman Empire to Weimar Germany. Ben reveals his hidden libertarian 'Gold Bug' tendencies.

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    1 h y 17 m
  • The nuclear renaissance
    Jan 30 2026

    In the mid twentieth century, nuclear power was meant to be the cheap and clean energy of the future. Now, nuclear power is expensive, maligned and unpopular. Ben, Sam and Alex discuss what went wrong in most of the world and, surprisingly, what went right in France. Ben delivers a radioactive hot take that meltdowns aren't so bad after all.

    You can read more about the French nuclear success here: https://www.worksinprogress.news/p/liberte-egalite-radioactivite

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    1 h y 21 m
  • The first cancer vaccine
    Dec 22 2025

    Hepatitis B is a tiny virus that causes hundreds of thousands of deaths from liver disease and cancer each year. The vaccine against it became the first of many milestones: it was the first viral protein subunit vaccine, the first recombinant vaccine, and the first vaccine to prevent a type of cancer.

    In this episode, Jacob and Saloni follow the trail of strange jaundice outbreaks that scientists traced to a stealthy liver virus, how scientists turned one viral surface protein into a lifesaving shot for newborns, and how it was all built upon breakthroughs in immunology.

    Hard Drugs is a new podcast from Works in Progress and Coefficient Giving 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:

    • Paul Offit (2007) Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases
    • Arthur M Silverstein (2009) A history of immunology
    • Ronald W Ellis (1993) Hepatitis B Vaccines in Clinical Practice
    • Sally Smith Hughes (2011) Genentech: The beginnings of biotech

    Articles:

    • Timothy M. Block et al. (2016) A historical perspective on the discovery and elucidation of the hepatitis B virus https://doi.org/10.1016/j.antiviral.2016.04.012
    • Naijuan Yao et al. (2022) Incidence of mother-to-child transmission of hepatitis B in relation to maternal peripartum antiviral prophylaxis: A systematic review and meta-analysis https://doi.org/10.1111/aogs.14448
    • Jill Koshiol et al. (2019) Beasley’s 1981 paper: The power of a well-designed cohort study to drive liver cancer research and prevention https://pmc.ncbi.nlm.nih.gov/articles/PMC5866222/
    • William J. McAleer et al. (1984) Human hepatitis B vaccine from recombinant yeast https://doi.org/10.1038/307178a0
    • Chunfeng Qu et al. (2014) Efficacy of Neonatal HBV Vaccination on Liver Cancer and Other Liver Diseases over 30-Year Follow-up of the Qidong Hepatitis B Intervention Study: A Cluster Randomized Controlled Trial https://doi.org/10.1371/journal.pmed.1001774
    • Anthony R Rees (2020) Understanding the human antibody repertoire https://doi.org/10.1080/19420862.2020.1729683

    Correction: Urea was mentioned as a protein, but is actually the product of a protein breakdown process, not a protein itself.

    Acknowledgements:

    • Aria Babu, editor at Works in Progress
    • Graham Bessellieu, video editor
    • Abhishaike Mahajan, cover art
    • Atalanta Arden-Miller, art direction
    • David Hackett, composer

    Works in Progress & Coefficient Giving

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    2 h y 59 m
  • The history of vaccines
    Nov 26 2025

    Before vaccines became routine, they were risky experiments. In this episode, Jacob and Saloni travel back to the world of smallpox, cowpox, and cow-based “vaccine farms” to see how scientists stumbled toward the first vaccines against infectious diseases: smallpox, rabies, TB, polio, and more. Through the stories of milkmaids and aristocrats, secret lab notebooks, microscopes and cell culture, they explore how trial and error turned gruesome folk practices into the science of immunization, and how it all began with a single pustule.

    Hard Drugs is a new podcast from Works in Progress and Coefficient Giving 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:

    • Gerald Geison (1995) The private science of Louis Pasteur
    • Thomas D. Brock (1998) Robert Koch: a life in medicine and bacteriology
    • Mervyn Susser and Zena Stein (2009) Eras in epidemiology : the evolution of ideas
    • Angela Leung (2011) Chapter: “Variolation” and vaccination in late Imperial China, ca. 1570–1911. History of vaccine development by Stanley Plotkin
    • Florian Horaud (2011) Chapter: Viral vaccines and cell substrate. History of vaccine development by Stanley Plotkin
    • Samuel Katz (2011) Chapter: The role of tissue culture in vaccine development. History of vaccine development by Stanley Plotkin
    • Hervé Bazin (2011) Chapter: Pasteur and the birth of vaccines made in the laboratory. History of vaccine development by Stanley Plotkin

    Articles:

    • Andrew Shattock et al. (2024) Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00850-X/fulltext
    • Saloni Dattani (2020) The story of Viktor Zhdanov https://worksinprogress.co/issue/the-story-of-viktor-zhdanov/
    • José Esparza et al. (2020) Early smallpox vaccine manufacturing in the United States https://doi.org/10.1016/j.vaccine.2020.05.037
    • Paula Gottdenker (1979) Francesco Redi and the fly experiments https://www.jstor.org/stable/44450950
    • Donald Angus Gillies (2016) Establishing causality in medicine and Koch’s postulates
    • Burt A Folkart (1993) Dr. Albert Sabin, Developer of Oral Polio Vaccine, Dies https://www.latimes.com/archives/la-xpm-1993-03-04-mn-283-story.html
    • Saloni Dattani (2025) Measles leaves children vulnerable to other diseases for years https://ourworldindata.org/measles-increases-disease-risk

    Acknowledgements:

    • Aria Babu, editor at Works in Progress
    • Graham Bessellieu, video editor
    • Abhishaike Mahajan, cover art
    • Atalanta Arden-Miller, art direction
    • David Hackett, composer

    Works in Progress & Coefficient Giving

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    2 h y 6 m
  • Should we ban ugly buildings?
    Nov 24 2025

    The YIMBY movement is divided about whether there is a tradeoff between building more homes and building beautifully. Ben, Sam and Samuel talk about how aesthetic regulations can make building more popular by generating goodwill from the public and decreasing appetite for historic preservation and how one can differentiate between good-faith complaints and pretextual arguments that make buildings economically unviable.

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    1 h y 19 m
  • The economics of the baby bust with Jesús Fernández-Villaverde
    Nov 6 2025

    Why are birth rates plummeting across the developing world? Why should we even care about the baby bust? Where can we find the most elastic baby? Jesús Fernández-Villaverde, Professor of Economics at the University of Pennsylvania, explains why Japan’s decline might be the best case scenario, the problems with childcare subsidies, why you shouldn’t study David Hume, and why the real fertility crisis isn't in rich countries.


    You can find Jesús on Twitter (https://x.com/JesusFerna7026/) where he tweets about on economics, history, and demographics, and read about Korea's fertility crisis in the new print edition of Works in Progress http://worksinprogress.co/print.

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    1 h y 23 m