Works in Progress

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Channel • 2 Shows

Science

Science

Updated 12/22/2025
Technology

Technology

Updated 12/22/2025

12/22/2025

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. 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 Conclusion 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

12/22/2025

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2h 59m
12/22/2025

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

12/22/2025

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2h 59m
11/06/2025

The economics of the baby bust with Jesús Fernández-Villaverde

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.

11/06/2025

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1h 23m
10/29/2025

Will AI solve medicine?

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 Intro0:09:56 Drug discovery1:02:20 Animal models1:49:09 Drug efficacy2:32:56 Drug safety2:58:29 Manufacturing and healthcare3:43:23 R&D funding4:00:56 Trust and ambition4:16:01 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 biotechTheses: 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 ProgressGraham Bessellieu, video editorAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy [Minor correction: Since the 1980s, malaria challenge trials no longer involve hundreds of bites; in the past, volunteers received many bites for the exposure part of the trial rather than the challenge part.]

10/29/2025

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4h 35m
11/24/2025

Should we ban ugly buildings?

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.

11/24/2025

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1h 19m
11/26/2025

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

11/26/2025

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2h 6m
10/24/2025

Treating cost disease with Congressman Jake Auchincloss

How can we build new cities in America? Which historical president is Trump most like? Why did immigration policy go so wrong? Sam and Pieter sit down with Congressman Jake Auchincloss to discuss the politics of the Abundance movement. They talk about Auchincloss's fight against free parking, regulating big tech, the success of YIMBYs, and why curing Alzheimers should be the next American moonshot project. Read more about some of the things they talked about:How Madrid built its metro cheaply: https://worksinprogress.co/issue/how-madrid-built-its-metro-cheaply/How France achieved the world's fastest nuclear buildout: https://worksinprogress.co/issue/liberte-egalite-radioactivite/The Housing Theory of Everything: https://worksinprogress.co/issue/the-housing-theory-of-everything/ Subscribe to the Works in Progress magazine here: https://worksinprogress.co/print/

10/24/2025

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58 min
10/29/2025

Will AI solve medicine?

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 Intro0:09:56 Drug discovery1:02:20 Animal models1:49:09 Drug efficacy2:32:56 Drug safety2:58:29 Manufacturing and healthcare3:43:23 R&D funding4:00:56 Trust and ambition4:16:01 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 biotechTheses: 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 ProgressGraham Bessellieu, video editorAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy

10/29/2025

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4h 35m
11/26/2025

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

11/26/2025

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2h 6m
09/26/2025

How traffic modernism ruined cities with Nicholas Boys Smith

Nicholas Boys Smith joins Ben and Sam to explain how to plan spaces that people like; dense, sociable and, above all else, beautiful. He says people don't like new buildings because they don't trust what planners and architects are going to do to the places that matter to them. As an alternative he presents his playbook for how YIMBYs can win over the public. If you liked this episode, you'll enjoy our first episode on The Great Downzoning: https://www.youtube.com/watch?v=LAcEfeLlqLo For more from Works in Progress: worksinprogress.co/print

09/26/2025

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1h 13m

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

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Works in Progress

Top Shows

The first cancer vaccine

The first cancer vaccine

The economics of the baby bust with Jesús Fernández-Villaverde

Will AI solve medicine?

Should we ban ugly buildings?

The history of vaccines

Treating cost disease with Congressman Jake Auchincloss

Will AI solve medicine?

The history of vaccines

How traffic modernism ruined cities with Nicholas Boys Smith

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