The first cancer vaccine

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Dec 22, 2025

Dive into the fascinating journey of the hepatitis B vaccine, the world's first cancer-preventing vaccine. Discover how early detective work linked mysterious jaundice outbreaks to a stealthy liver virus. Learn about the groundbreaking science that turned viral proteins into lifesaving shots, with a thrilling behind-the-scenes look at the controversial trials and the scientists who revolutionized immunology. This episode highlights the immense impact of vaccination on public health, including remarkable reductions in liver cancer rates.

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ADVICE

Favor Universal Newborn Vaccination

Prefer universal newborn HBV vaccination because screening can miss cases and uptake falls with complexity.
Early birth dose prevents chronic infections and reduces long-term cancer risk.

ANECDOTE

Krugman's Controversial Vaccine Tests

Saul Krugman injected inactivated patient serum into institutionalized children and showed heated serum could protect against hepatitis.
His experiments demonstrated the protective role of the surface antigen but are now ethically controversial.

ANECDOTE

Hilleman's Plasma Purification Tale

Morris Hilleman sourced high-risk plasma and used pepsin, urea, and formaldehyde to strip infectivity while preserving surface antigen.
That process reduced infectious HBV by ~10^15-fold and produced a near-pure antigen product.

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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