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 biotechArticles: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

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.Chapters:0:00:00 Introducing the hepatitis B vaccine0:15:46 The mysterious trail of jaundice outbreaks0:28:03 How a tiny virus causes cirrhosis and liver cancer0:53:19 Maurice Hilleman's purified hep B vaccine1:17:36 Turning the hep B vaccine recombinant1:29:14 The impact of hep B vaccination1:39:27 The 19th century battle for immunology2:01:34 How the body makes an almost infinite number of antibodies2:30:57 How subunit vaccines took over2:45:33 ConclusionSaloni’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 biotechArticles: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

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 PlotkinArticles: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

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 PlotkinArticles: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

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.