Works in Progress Podcast

Works in Progress is an online magazine devoted to new and underrated ideas about economic growth, scientific progress, and technology. Subscribe to listen to the Works in Progress podcast, plus Hard Drugs by Saloni Dattani and Jacob Trefethen.

  1. Should everyone be taking statins?

    2 DAYS AGO

    Should everyone be taking statins?

    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, composer Works in Progress & Coefficient Giving Books Daniel Steinberg (2007) The Cholesterol Wars.Jie Jack Li (2009) Triumph of the Heart: The Story of Statins. Blog posts James Stein (2025) Lipid and lipoprotein basics series. https://jamesstein18.substack.com/p/part-i-lipid-and-lipoprotein-basics  Articles Akira 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  Videos Ninja Nerd (2018) Lipoprotein metabolism https://www.youtube.com/watch?v=wQY0xpwqPfQ

    2h 55m
  2. The first cancer vaccine

    22/12/2025

    The first cancer vaccine

    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 DiseasesArthur M Silverstein (2009) A history of immunologyRonald W Ellis (1993) Hepatitis B Vaccines in Clinical PracticeSally 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.14448Jill 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 ProgressGraham Bessellieu, video editorAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Coefficient Giving

    2h 59m
  3. The history of vaccines

    26/11/2025

    The history of vaccines

    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 PasteurThomas D. Brock (1998) Robert Koch: a life in medicine and bacteriologyMervyn Susser and Zena Stein (2009) Eras in epidemiology : the evolution of ideasAngela Leung (2011) Chapter: “Variolation” and vaccination in late Imperial China, ca. 1570–1911. History of vaccine development by Stanley PlotkinFlorian Horaud (2011) Chapter: Viral vaccines and cell substrate. History of vaccine development by Stanley PlotkinSamuel Katz (2011) Chapter: The role of tissue culture in vaccine development. History of vaccine development by Stanley PlotkinHervé 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 postulatesBurt 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 ProgressGraham Bessellieu, video editorAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Coefficient Giving

    2h 6m

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Works in Progress is an online magazine devoted to new and underrated ideas about economic growth, scientific progress, and technology. Subscribe to listen to the Works in Progress podcast, plus Hard Drugs by Saloni Dattani and Jacob Trefethen.

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