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Hard Drugs

Hard Drugs

Von: Saloni Dattani & Jacob Trefethen
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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.Works in Progress Magazine © 2025 Hygiene & gesundes Leben Wissenschaft
  • The art of protein design with AI
    Oct 15 2025

    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 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


    Subscribe to the Works in Progress print magazine: https://worksinprogress.co/print/

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    1 Std.
  • Hacking proteins with AI
    Oct 1 2025

    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 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


    Subscribe to the Works in Progress print magazine: https://worksinprogress.co/print/

    Mehr anzeigen Weniger anzeigen
    55 Min.
  • 100 years of insulin in 15 minutes
    Sep 16 2025

    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 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

    Mehr anzeigen Weniger anzeigen
    18 Min.
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