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 SummaryBlogposts: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
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4:34:48
The art of protein design with AI
What if you could design a protein never seen in nature? 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 ProgressGraham Bessellieu, video editorRachel Shu, on-site editorAnna Magpie, fact-checkingAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy
Subscribe to the Works in Progress print magazine: https://worksinprogress.co/print/
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1:00:21
Hacking proteins with AI
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 ProgressGraham Bessellieu, video editorRachel Shu, on-site editorAnna Magpie, fact-checkingAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy
Subscribe to the Works in Progress print magazine: https://worksinprogress.co/print/
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54:36
100 years of insulin in 15 minutes
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/ Subscribe to the Works in Progress print magazine: https://worksinprogress.co/print/Books:Genentech: The beginnings of biotech by Sally Smith HughesArticles: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 ProgressAdrian Bradley, on-site producerAnna Magpie, fact-checkingAbhishaike Mahajan, cover artAtalanta Arden-Miller, art directionDavid Hackett, composerWorks in Progress & Open Philanthropy
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Proteins: Weird blobs that do important things
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]
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Hard Drugs is a show by Saloni Dattani and Jacob Trefethen about medical innovation: how to speed it up, how to scale it up, and how to make sure lifesaving tools reach the people who need them the most. It is brought to you by Works in Progress and Open Philanthropy.
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