220: How Medical Innovation Really Works: Friction, Failure, and Forward Motion

On this episode of The Innovation Storytellers Show, I sit down with Dr. William Pao, physician scientist, former Chief Development Officer at Pfizer, and author of Breakthrough – The Quest for Life-Changing Medicines. His journey into medicine began with the loss of his father to cancer when he was just 13 years old, a moment that shaped his life’s mission to develop treatments that change outcomes for patients everywhere.

We explore the extraordinary, and often invisible, process of medical innovation. Dr. Pao takes us behind the scenes of eight real-world breakthroughs, revealing the persistence, failures, and unexpected turns that happen long before a drug reaches the market. He shares the story of a 15-year effort to create an HIV capsid inhibitor now given just twice a year, and how a combination of basic science curiosity and problem-solving under pressure turned a limitation into a breakthrough.

We dive into the development of CRISPR-based therapies for sickle cell disease and thalassemia, a century-long scientific journey that required insights from genetics, epidemiology, and bioengineering before it could cure patients.

Throughout our conversation, Dr. Pao brings these stories to life with the human elements that make them possible. We talk about the “killer experiment” mindset that helps teams decide whether to keep going or shut a project down, the value of institutional memory, and why innovation in medicine requires a rare mix of biological insight, clinical understanding, and technological advancement.

We also explore the emotional side of the work, how innovators cope with fatigue, navigate internal resistance, and make hard calls when decades of work are on the line.

Whether you are developing life-saving drugs or leading innovation in a completely different field, you will find practical lessons here. Dr. Pao’s experiences show how to work through uncertainty, keep an open mind to ideas from outside your domain, and maintain the discipline to make good decisions even when the stakes are high.