Works in Progress Podcast

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

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

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.

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.

Artificial intelligence is transforming how we discover and develop new medicines. But how far can it really take us? In this episode, Jacob and Saloni trace the path of drug development from discovery to testing, manufacturing, and delivery. They explore where AI could speed things up, and where it still hits the limits of biology, data, and economics. They ask what it would take, beyond algorithms, to actually cure and eradicate diseases.
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/ 
Chapters:
0:00:00 Intro
0:09:56 Drug discovery
1:02:20 Animal models
1:49:09 Drug efficacy
2:32:56 Drug safety
2:58:29 Manufacturing and healthcare
3:43:23 R&D funding
4:00:56 Trust and ambition
4:16:01 Summary
Blogposts:
Claus Wilke (2025) We still can’t predict much of anything in biology https://blog.genesmindsmachines.com/p/we-still-cant-predict-much-of-anything 
Elliot Hershberg (2025) What are virtual cells? https://centuryofbio.com/p/virtual-cell 
Jacob Trefethen (2025) Blog series. 1) What does AI progress mean for medical progress? https://blog.jacobtrefethen.com/ai-progress-medical-progress/ 2) AI will not suddenly lead to an Alzheimer’s cure https://blog.jacobtrefethen.com/ai-san-francisco/ 3) AI could help lead to an Alzheimer’s cure https://blog.jacobtrefethen.com/ai-optimism/ 
Articles:
Wendi Yan (2024) Discovering an antimalarial drug in Mao’s China https://www.asimov.press/p/antimalarial-drug 
Jason Crawford (2020) Innovation is not linear https://worksinprogress.co/issue/innovation-is-not-linear/ 
Shayla Love (2025) An ‘impossible’ disease outbreak in the Alps https://www.theatlantic.com/health/archive/2025/03/als-outbreak-montchavin-mystery/682096/ 
Alex Telford (2024) Origins of the lab mouse https://www.asimov.press/p/lab-mouse 
Jonathan Karr et al. (2012) A whole-cell computational model predicts phenotype from genotype https://pmc.ncbi.nlm.nih.gov/articles/PMC3413483/ 
Wen-Wei Liao et al. (2023) A draft human pangenome reference https://www.nature.com/articles/s41586-023-05896-x 
Per-Ola Carlsson (2025) Survival of transplanted allogeneic beta cells with no immunosuppression https://www.nejm.org/doi/pdf/10.1056/NEJMoa2503822 
Saloni Dattani (2024) Antipsychotic medications: a timeline of innovations and remaining challenges https://ourworldindata.org/antipsychotic-medications-timeline 
Saloni Dattani (2024) What was the Golden Age of antibiotics, and how can we spark a new one? https://ourworldindata.org/golden-age-antibiotics 
Books:
Sally Smith Hughes (2011) Genentech: The beginnings of biotech
Theses:
Alvaro Schwalb (2025). Estimating the burden of Mycobacterium tuberculosis infection and the impact of population-wide screening for tuberculosis.
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 & Open Philanthropy