Before the twentieth century, most cities were highly permissive about what people were allowed to build on their land. Nearly all Western householders lost these liberties during the first half of the twentieth century. Samuel Hughes calls this phenomenon The Great Downzoning. In the first episode of the Works in Progress Podcast, he describes how and why this happened, and what it means for modern pro-housing campaigners.

Lenacapavir is a new HIV drug that blocks infections with an efficacy rate of nearly 100%, and it could completely change the fight against HIV worldwide. Saloni and Jacob talk about the development and prospects for this new drug, as well as the history of HIV, the initial discovery of retroviruses, and how HIV was transformed from a death sentence to a manageable condition.

Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.

00:00 Intro
03:52 How was HIV discovered? Where did it come from, and how does it attack the body and cause AIDS?
38:10 Antiretrovirals: How did scientists develop breakthrough HIV drugs — from azidothymidine to protease inhibitors to PrEP?
1:51:35 How does prevention and treatment work today?
2:19:03 HIV’s capsid and the breakthrough of lenacapavir, the first-approved HIV capsid inhibitor
2:50:36 How to develop long-lasting treatments
3:14:45 Lenacapavir’s near 100% efficacy in clinical trials
3:48:40 The impact of global programs against HIV, and can we now end HIV?

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/ 

Books:

• How to Survive a Plague — by David France (2016). [Mentioned as a history of the science and activism against the AIDS epidemic, and the protease-inhibitor breakthrough.] https://surviveaplague.com/ 
• And the Band Played On — Randy Shilts (1987). [Mentioned as an account of the early years of AIDS.] https://us.macmillan.com/books/9780312374631/andthebandplayedon/ 
• Drug development stories: From bench to bedside — Elsevier (2024). [Mentioned as containing a history of the development of lenacapavir] https://shop.elsevier.com/books/drug-discovery-stories/yu/978-0-443-23932-8 

Retrospectives:

• The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic — Samuel Broder (2015). https://doi.org/10.1016/j.antiviral.2009.10.002 
• History of the discoveries of the first human retroviruses: HTLV-1 and HTLV-2 — Robert Gallo (2005). https://doi.org/10.1038/sj.onc.1208980 
• A Look at Long Acting Drugs — Anne de Bruyn Kops for Open Philanthropy (2025). https://bit.ly/long-acting-drugs-op 
• How To Save Twenty Million Lives, with Dr Mark Dybul — Statecraft (2023)  https://www.statecraft.pub/p/saving-twenty-million-lives 
• The Road to Fortovase. A History of Saquinavir, the First Human Immunodeficiency Virus Protease Inhibitor — Redshaw et al. (2000) https://link.springer.com/chapter/10.1007/978-3-642-57092-6_1 

Articles:

• The origin of genetic diversity in HIV-1 — Smyth et al. (2012). [Mentioned as a review about HIV’s recombination, which described it as “a primitive form of sexual reproduction”] https://www.sciencedirect.com/science/article/pii/S0168170212002122 
• PF74 Reinforces the HIV-1 Capsid To Impair Reverse Transcription-Induced Uncoating — Rankovic et al. (2018) https://doi.org/10.1128/JVI.00845-18 
• Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons — Kelley et al. (2024) https://www.nejm.org/doi/full/10.1056/NEJMoa2411858 
• Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women — Bekker et al. (2024) https://www.nejm.org/doi/10.1056/NEJMoa2407001 
• The evolution of HIV-1 and the origin of AIDS — Sharp and Hahn (2010) https://doi.org/10.1098/rstb.2010.0031 
• Pathogenic mechanisms of HIV disease — Moir et al. (2011) https://doi.org/10.1146/annurev-pathol-011110-130254 
• Estimating per-act HIV transmission risk: a systematic review — Patel et al. (2012) https://journals.lww.com/aidsonline/fulltext/2014/06190/Estimating_per_act_HIV_transmission_risk__a.14.aspx 
• The structural biology of HIV-1: mechanistic and therapeutic insights — Engelman and Cherepanov (2012) https://doi.org/10.1038/nrmicro2747 
• Challenges and opportunities in the development of complex generic long-acting injectable drug products — O’Brien et al. (2021) https://doi.org/10.1016/j.jconrel.2021.06.017 
• Making a “Miracle” HIV Medicine — Nahas (2025) https://press.asimov.com/articles/hiv-medicine 
• Highly active antiretroviral therapy transformed the lives of people with HIV — Dattani (2024) https://ourworldindata.org/data-insights/highly-active-antiretroviral-therapy-transformed-the-lives-of-people-with-hiv 
• 
  

Videos:

• Mini-Lecture Series: HIV Capsid Inhibitors: Mechanism of Action — David Spach, National HIV Curriculum (2024) https://www.youtube.com/watch?v=iZ9KDxV5Zbs&ab_channel=NationalHIVCurriculum 

Image credits:

• Mini-Lecture Series: HIV Capsid Inhibitors: Mechanism of Action — David Spach, National HIV Curriculum (2024) [Multiple diagrams of HIV capsid and lenacapavir’s effect.]
• Saloni Dattani; Our World in Data (2024) Highly active antiretroviral therapy transformed the lives of people with HIV. [Graph of decline in HIV/AIDS mortality after HAART was introduced.]
• Engelman and Cherepanov (2012). The structural biology of HIV-1: mechanistic and therapeutic insights. [Diagram of HIV’s entry into the cell.]
• Susan Moir, Tae-Wook Chun, Anthony S Fauci (2011). Pathogenic mechanisms of HIV disease. [Diagram of HIV replication rates over time, contrasting acute and chronic infection.]
• Saloni Dattani, adapted from Patel et al. (2014). Estimating per-act HIV transmission risk: a systematic review. [Bar chart of risks of contracting HIV from different sources when unprotected.]
• Thomas Splettstoesser under CC-BY. [Diagram of HIV’s internal structure.]
• Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women — Bekker et al. (2024) [Chart of lenacapavir’s efficacy.]
• Our World in Data based on Joint United Nations Programme on HIV/AIDS (2024). [Chart of global HIV deaths over time.]

Acknowledgements:

• Douglas Chukwu, researcher at Open Philanthropy
• Sanela Rankovic, Acting Instructor at the In...

Why does London dominate Britain's economy, whereas Germany's is spread out across the whole country? Why don't restaurants scale well? What kind of social science research (if any) should the government be funding? Stian Westlake – Executive Chair of the Economic and Social Research Council and author of Capitalism Without Capital: The Rise of the Intangible Economy – joins the Works in Progress podcast to discuss these questions.

Historian Anton Howes discusses how Henry VIII turned Britain into an economic backwater – making it the unlikeliest place for the Industrial Revolution to happen. But, he explains it only took a small cabal of people who understood the problems of the time to turn the fate of the country (and thus, the world) around.

You can learn more about the history of the Industrial Revolution on Anton's Substack, Age of Invention. And you can learn more about progress at Works in Progress. 

Why is Chinese housing so expensive despite being oversupplied? How did land reforms in Russia lead to the Bolshevik revolution? What killed Georgism? The Economist’s Wall Street Editor, Mike Bird, discusses the underrated economics of land.

You can preorder Mike's book here and read more about land readjustment in Works in Progress Issue 19.

This episode kicks off a mini-series on proteins, drug development and AI. Saloni and Jacob explore the world of proteins, including how proteins fold into complex shapes, why that complexity matters and how crowded and dynamic the inside of a cell really is; and they exchange surprising statistics about proteins.

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/ 

Books:

• Ron Milo and Rob Phillips. Biology by the numbers https://book.bionumbers.org/ 
• Carl Ivar Branden and John Tooze (1999) Introduction to protein structure https://www.taylorfrancis.com/books/mono/10.1201/9781136969898/introduction-protein-structure-john-tooze-carl-ivar-branden 

Articles:

• Niko McCarty (2023). Biology is a burrito. https://www.asimov.press/p/burrito-biology  
• Rhiannon Morris, Katrina Black, and Elliott Stollar (2022) Uncovering protein function: from classification to complexes. https://pmc.ncbi.nlm.nih.gov/articles/PMC9400073/ 
• Victor Muñoz and Michele Cerminara (2016) When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches https://portlandpress.com/biochemj/article/473/17/2545/49248/When-fast-is-better-protein-folding-fundamentals 

Image credits:

• Chang et al. (2012) Egg white in organic electronics. https://spie.org/news/4149-egg-white-in-organic-electronics [diagram of egg white denaturing and cross-linking]
• John Kendrew’s model of myoglobin’s structure; via Carl Ivar Branden and John Tooze (1999) Introduction to protein structure.
• Carl Ivar Branden and John Tooze (1999) Introduction to protein structure. [diagram of amino acids and protein structure]
• Ron Milo and Rob Phillips. Which is bigger, mRNA or the protein it codes for? https://book.bionumbers.org/which-is-bigger-mrna-or-the-protein-it-codes-for/ [diagram of myoglobin mRNA vs protein]

Scitable (2014). Microtubules and Filaments. https://www.nature.com/scitable/topicpage/microtubules-and-filaments-14052932/ [diagram of microtubules]

Is it better to be run by engineers, lawyers or regulators? Can you build an economy on luxury handbags or do you need advanced manufacturing? Dan Wang, author of Breakneck: China's Quest to Engineer the Future discusses why China outbuilds America, how the young and ambitious succeed in China, and the secret to finding the best Chinese restaurants.

You can order his new book here, read his annual letters on China here, and check out London's best Suzhou noodles here.
If you want more from Works in Progress you can read the magazine here or listen to our episode about land in East Asia here.

Social scientist Alice Evans talks about why, despite a superficially similar feminist movement in East Asia, Western feminism has been much successful. Alice, Sam and Aria talk about dating markets, drinking culture at work, top-down media control, and what tax policy is best for motivating people to have more children.

For more of Alice's work, check out her Substack.

Go to worksinprogress.co to read more from Works in Progress.

References

• Flowers of Fire: The Inside Story of South Korea's Feminist Movement and What It Means for Women' s Rights Worldwide Paperback by Hawon Jung
• The clan and the corporation: Sustaining cooperation in China and Europe by Avner Greif and Guido Tabellini
• The Swedish Theory of Love: Individualism and Social Trust in Modern Sweden by Henrik Berggren  and Lars Trägårdh
• Drunk: How We Sipped, Danced, and Stumbled Our Way to Civilization Hardcover by Edward Slingerland

A hundred years ago, insulin was scraped from pig pancreases. Today, it’s made by bacteria in giant tanks. In the second part of a mini series on proteins, drug development and AI, Saloni tells the story of how insulin went from a crude animal extract to the first genetically-engineered drug, kickstarting the biotech industry along the way.

Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/ 

Books:

• Genentech: The beginnings of biotech by Sally Smith Hughes

Articles:

• FDA (2007). Celebrating a Milestone: FDA's Approval of First Genetically-Engineered Product https://fda.report/media/110447/Celebrating-a-Milestone--FDA%27s-Approval-of-the-First-Genetircally-Engineered-Product.pdf 
• Genentech (2016). Cloning Insulin https://www.gene.com/stories/cloning-insulin 
• Arthur Riggs (2020). Making, Cloning, and the Expression of Human Insulin Genes in Bacteria: The Path to Humulin https://academic.oup.com/edrv/article/42/3/374/6042201 

Podcasts:

• Novo Nordisk (Ozempic) by the Acquired podcast https://www.acquired.fm/episodes/novo-nordisk-ozempic 

Acknowledgements:

• Aria Babu, editor at Works in Progress
• Adrian Bradley, on-site producer
• Anna Magpie, fact-checking
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David Hackett, composer

Works in Progress & Open Philanthropy

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

Nature didn’t evolve all the proteins we need, but maybe artificial intelligence can help. Jacob and Saloni explore how tools like AlphaFold and ProteinMPNN are helping researchers re-engineer proteins, to make them safer, more stable, and more effective. They talk about how new technologies could help make a long-sought vaccine against Strep A, which causes scarlet fever and rheumatic heart disease, and how similar tools have already led to breakthroughs against COVID and RSV.

Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/ 

Courses:

• EMBL-EBI. AlphaFold: A practical guide https://www.ebi.ac.uk/training/online/courses/alphafold/ 

Articles:

• Monica Jain et al. (2022) Exosite binding modulates the specificity of the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease. https://pmc.ncbi.nlm.nih.gov/articles/PMC9464890/ 
• Jakki Cooney et al. (2008) Crystal structure of C5a peptidase https://www.rcsb.org/structure/3EIF 
• Hui Li et al. (2017) Mutagenesis and immunological evaluation of group A streptococcal C5a peptidase as an antigen for vaccine development and as a carrier protein for glycoconjugate vaccine design https://pubs.rsc.org/en/content/articlelanding/2017/ra/c7ra07923k 

Lectures:

• Rosetta Commons (2024) AlphaFold – ML for protein structure prediction https://www.youtube.com/watch?v=SVrn8_8aKO8 
• Rosetta Commons (2024) MPNN – ML for protein sequence design https://www.youtube.com/watch?v=6z4XmUAwdNA 

Acknowledgements:

• Aria Babu, editor at Works in Progress
• Graham Bessellieu, video editor
• Rachel Su, on-site editor
• Anna Magpie, fact-checking
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David Hackett, composer

Works in Progress & Open Philanthropy

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/

What if you could design a protein never seen before? In this episode, Jacob and Saloni explore how researchers are using new tools like RFDiffusion, AlphaFold, and ProteinMPNN to ‘hallucinate’ entirely novel proteins: designing them from scratch to solve problems evolution hasn’t tackled. They talk about how these technologies could transform medicine, agriculture, and materials science. Along the way, they reflect on the surprising ways AI is changing the process of science itself.

Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen.

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/ 

Courses:

• EMBL-EBI. AlphaFold: A practical guide https://www.ebi.ac.uk/training/online/courses/alphafold/ 

Articles:

• Tanja Kortemme (2024) De novo protein design—From new structures to programmable functions https://www.cell.com/cell/fulltext/S0092-8674(23)01402-2 
• Jie Zhu et al. (2021) Protein Assembly by Design https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00308 

Lectures:

• Rosetta Commons (2024) Diffusion models for protein structure generation (and design) https://www.youtube.com/watch?v=OEnY2yA3jy8 
• Rosetta Commons (2024) AlphaFold – ML for protein structure prediction https://www.youtube.com/watch?v=SVrn8_8aKO8 
• Rosetta Commons (2024) MPNN – ML for protein sequence design https://www.youtube.com/watch?v=6z4XmUAwdNA 

Acknowledgements:

• Aria Babu, editor at Works in Progress
• Graham Bessellieu, video editor
• Rachel Shu, on-site editor
• Anna Magpie, fact-checking
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David Hackett, composer

Works in Progress & Open Philanthropy

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

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.

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.

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

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

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

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. 

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 Introduction
13:35 The decline in heart disease mortality
31:02 Surprising facts about cholesterol
55:40 The lipid hypothesis: 7 lines of evidence for the harms of LDL cholesterol
1:22:15 How cholesterol works
1:30:40 The discovery of statins
1:48:44 Should everyone be on statins?
1:57:10 PCSK9 drugs and beyond
2:22:56 Summary 

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/ 

Acknowledgements:

• Aria Babu, editor at Works in Progress
• Graham Bessellieu, video editor
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David 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.94.9.4312
• Saloni Dattani (2025) Death rates from cardiovascular disease have fallen dramatically — what were the breakthroughs behind this? https://ourworldindata.org/cardiovascular-deaths-decline
• Cholesterol 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)61350-5
• E. 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 

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. 

Every hundred South Koreans today will have only six great-grandchildren between them. The rest of the world can learn from Korea’s catastrophe to avoid the same fate.

You can see the images, graphs and read the article at https://worksinprogress.co/issue/two-is-already-too-many/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Phoebe Arslanagic-Little
Read by Stuart Ritchie
Music by David Hackett

There are some animals that can live for hundreds of years. Do the secrets to human longevity lie in a lobster's ability to regrow felled limbs, in a Greenland shark's ultra-slow metabolism, or in an elephant's extreme cancer resistance? Aria, Ben and Saloni discuss why human (and pet) lifespans have increased so much over the past centuries and what we else we can do to age more slowly.

For more, read Aria's piece on longevity: https://worksinprogress.co/issue/the-perks-of-being-a-mole-rat/

Japan faced some of the world’s toughest planning problems. It solved them by letting homeowners replan whole neighborhoods privately by supermajority vote. You can see the images, graphs and read the article at https://worksinprogress.co/issue/how-to-redraw-a-city/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Anya Martin
Read by Stuart Ritchie
Music by David Hackett

Radiology combines digital images, clear benchmarks, and repeatable tasks. But replacing humans with AI is harder than it seems. You can see the images, graphs and read the article at https://worksinprogress.co/issue/the-algorithm-will-see-you-now/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Deena Mousa
Read by Stuart Ritchie
Music by David Hackett

There are basically no ugly buildings from before 1930. There are definitely none from before 1830. Why? Is it survivorship bias? Have we demolished all the ugly old buildings and only kept the most beautiful and prestigious buildings? Is it just a matter of taste? Perhaps we haven't come round to liking modern buildings yet but we will. Is it because ornament is too expensive to reproduce now labor costs are too high? Is it because ornament is too cheap because of mass manufacturing and elites want to signal distinction from poor people who can now afford to cover their buildings with ornament too? Samuel, Ben and Aria discuss the merits of these different theories and what actually makes some architecture beautiful. 

If you enjoyed this episode, you'll enjoy Samuels many essays on beauty in architecture.
Cheap ornament and status games: https://worksinprogress.co/issue/cheap-ornament-and-status-games/
The beauty of concrete: https://worksinprogress.co/issue/the-beauty-of-concrete/
Making architecture easy: https://worksinprogress.co/issue/making-architecture-easy/
Against the survival of the prettiest: https://worksinprogress.co/issue/against-the-survival-of-the-prettiest/

The world is warming faster than we can cut emissions. Volcanoes are already cooling the planet, with particles that reflect sunlight. Maybe we can too. You can see the images, graphs and read the article at https://worksinprogress.co/issue/sunscreen-for-the-planet/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Daniele Visioni & Dakota Gruener
Read by Stuart Ritchie
Music by David Hackett

If we ever want to live in space, we need to work out a way of creating artificial gravity.

You can see the images, graphs and read the article at https://worksinprogress.co/issue/inflatable-space-stations/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Angadh Nanjangud
Read by Stuart Ritchie
Music by David Hackett

We disinfect water before we drink it. Germicidal ultraviolet could make airborne disease as rare as those carried by water. You can see the images, graphs and read the article at https://worksinprogress.co/issue/the-death-rays-that-guard-life/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Gavriel Kleinwaks & Karam Elabd
Read by Stuart Ritchie
Music by David Hackett

You should freeze your eggs. Contrary to popular myth, egg freezing works very well and if you freeze your eggs in your twenties or early thirties, you have a very good chance of having a child.

European leaders are looking to copy Australia's example and cut migration from boat-bound refugees but they are in danger of learning the wrong lessons. Offshore detention was the most widely publicized aspect of their refugee policy but it didn't work. Turnbacks were much cheaper and more effective.

Ben, Aria and Pieter discuss different articles in the new issue of Works in Progress. They discuss how Britain lost its position as the world leader in nuclear power, why ASML is so successful, how envy killed the first bus, and how cool neo-traditional temples are.

Buy your copy here: https://worksinprogress.co/print/

Competition makes capitalism work. A new method for measuring it may be the holy grail of economic regulation.  You can see the images, graphs and read the article at https://worksinprogress.co/issue/how-to-spot-a-monopoly/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Brian Albrecht
Read by Stuart Ritchie
Music by David Hackett

English prose has become much easier to read. But shorter sentences had little to do with it. You can see the images, graphs and read the article at https://worksinprogress.co/issue/the-logical-triumph-of-english/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Henry Oliver
Read by Stuart Ritchie
Music by David Hackett

Drug development has never been more expensive, in terms of output per dollar spent. 

This trend, called Eroom's law, is surprising, considering incredible technological advances.

Ben and Saloni talk to Ruxandra Teslo about why this has happened and what can be done about it.

How can we reform clinical trials to make them more efficient and abundant? Why are so many pharma companies moving early trials to Australia? What's wrong with ethics boards and how can we fix them without compromising on safety?

Generations of microbes evolve in hours, not millennia. By speeding up Darwin’s clock, scientists have watched evolution happen in real time, and it’s changed how we understand natural selection. You can see the images, graphs and read the article at https://worksinprogress.co/issue/the-evolution-of-bacteria-2/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Kevin Blake
Read by Stuart Ritchie
Music by David Hackett

Local government works best when areas can compete with each other and capture some of the upside of economic growth. Ben sits down with Judge Glock to discuss how well-structured local incentives helped make Loudoun County, Virginia, the global capital of data centers — and helped France build so many nuclear power stations.

They discuss which public goods local government is best placed to provide, why America has better housing outcomes than its reputation suggests, and when national government needs to constrain local power.

Read Judge Glock's piece on why water in America is too clean here: https://worksinprogress.co/issue/the-gold-plating-of-american-water/

In 1965, married American women did 34 hours of housework weekly. By 2010, that had fallen to 18 hours. The dishwasher wasn’t the only cause, but it certainly helped. You can see the images, graphs and read the article at https://worksinprogress.co/issue/inventing-the-dishwasher/

And you can find the rest of Works in Progress at worksinprogress.co

Words by Erin Braid
Read by Stuart Ritchie
Music by David Hackett

The Trump administration wants to bolster traditional art. Their attempt to revive sculpture, a mass statue-building program, is doomed. America doesn’t have the sculptors, foundries, and workers to make hundreds of bronze or marble sculptures. North Korea would be in a much better position.

Sam and Samuel sit down with our Art Director, Atalanta, a sculptor by training, and talk all things sculpture. They discuss how art education has become de-skilled, how sculpture has always been the best art form for mass production and the surprising places the tradition has been kept alive. 

In the nineteenth century, cities often grew a thousandfold while increasing wages, the size of homes, and delivering great public goods like electricity and plumbing to their people. What made them so extraordinary? They had a hybrid of laissez-faire and top-down control. Landowners could build almost anything they liked but street networks were laid out with near-Soviet thoroughness decades in advance. Transport and utilities, meanwhile, ran as regulated monopolies. They were funded by users, turned a profit, but prices were controlled.

Samuel, Ben and Aria discuss what made this system work and why it was dismantled. 

Malaria is caused not by a virus or bacterium, but by a complex, shape-shifting parasite that has evolved alongside us for millennia. This has made vaccine development a brutal challenge.

In this episode, Jacob and Saloni are joined by Katharine Collins, who co-invented the second malaria vaccine, called R21, during her PhD. They discuss the gruelling process of reverse-engineering a vaccine and eureka moments along the way. They ask whether the biggest barriers to new vaccines are scientific or financial, and what it will take to finally eradicate one of natureʼs most vicious killers.

Hard Drugs is a podcast from Works in Progress 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/ 

Acknowledgements:

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

Works in Progress & Coefficient Giving 

Thesis

• Katharine Collins (2014). R21, a novel particle based vaccine for a multi-component approach to malaria vaccination.

Books

• R. Killick-Kendrick (2012). Rodent Malaria.
• Michael Kremer and Rachel Glennerster (2004). Strong Medicine: Creating Incentives for Pharmaceutical Research on Neglected Diseases.

Articles and reports

• Saloni Dattani (2023). Why we didn’t get a malaria vaccine sooner. https://worksinprogress.co/issue/why-we-didnt-get-a-malaria-vaccine-sooner/ 
• Jerome P Vanderberg (2010). Reflections on Early Malaria Vaccine Studies, the First Successful Human Malaria Vaccination, and Beyond https://pmc.ncbi.nlm.nih.gov/articles/PMC2637529/
• Pratik Pawar (2022). It Took 35 years to Get a Malaria Vaccine. Why? https://undark.org/2022/05/25/it-took-35-years-to-get-a-malaria-vaccine-why/ 
• Ernst R. Berndt, Rachel Glennerster, Michael R. Kremer, Jean Lee, Ruth Levine, Georg Weizsacker & Heidi Williams (2005) Advanced Purchase Commitments for a Malaria Vaccine: Estimating Costs and Effectiveness. https://www.nber.org/papers/w11288 
• Ryan Duncombe, Karam Elabd and Justin Sandefur (2024). Avoiding Another Lost Decade on Malaria Vaccines https://www.cgdev.org/publication/avoiding-another-lost-decade-malaria-vaccines