Works in Progress Podcast

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.

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.

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

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