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

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

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

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

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

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

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.