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Susan Desmond-Hellmann is a physician and scientist whose remarkable career has spanned clinical medicine, oncology, biotech innovation, and global health leadership. In this episode, Susan shares insights from her journey training in internal medicine during the early AIDS crisis, treating HIV-related cancers in Uganda, and developing groundbreaking cancer therapies like Herceptin and Avastin. She reflects on her leadership roles at UCSF and the Bill and Melinda Gates Foundation, offering lessons on guiding large-scale health initiatives, navigating uncertainty, and fostering scientific innovation. The conversation explores the promise of precision medicine, the integration of patient care and policy, and the evolving role of artificial intelligence in transforming diagnostics, drug development, and global access to care.

We discuss:

• Susan’s medical training, the start of the AIDS epidemic, and the transformative experiences that shaped her career [3:00];
• Susan’s experience working on the frontlines of the HIV/AIDS crisis in Uganda [12:30];
• Susan’s time working in general oncology and her transition to biotech where she helped develop taxol—a top-selling cancer drug [26:30];
• Genentech’s origins, and its groundbreaking use of recombinant DNA to develop biologic drugs [33:45];
• Susan’s move to Genentech, and her pivotal role in the development and success of Herceptin as a groundbreaking therapy in targeted oncology [44:00];
• The rise of antibody-based cancer therapies: the development of Rituxan and Avastin [52:15];
• The step-by-step drug development process and the scientific and strategic challenges involved [1:01:30];
• The ethical and economic controversy surrounding Avastin’s high cost and limited survival benefit [1:12:30];
• Susan’s tenure as chancellor at UCSF: leading during a financially strained period, and her strategic approach to fundraising and institutional development [1:14:45];
• What Susan learned as CEO of the Bill and Melinda Gates Foundation: strategic processes and decision-making frameworks [1:26:00];
• Susan’s philosophy of leadership and how she sought to build an empowering, values-driven culture at the Gates Foundation [1:35:15];
• The erosion of public trust in science during COVID, the communication failures around controversial treatments like ivermectin, and the need for better public health engagement and transparency [1:39:30];
• The role of AI in transforming medicine: from drug development to cancer detection and beyond [1:53:00]; and
• More.

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View the Show Notes Page for This Episode

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Sean Mackey is a professor of pain medicine at Stanford University and the director of the Stanford Systems Neuroscience and Pain Lab, where his research explores the neural mechanisms of pain and the development of novel treatments for chronic pain. In this episode, Sean joins Peter for a wide-ranging discussion on the multifaceted nature of pain—as both a sensory and emotional experience—and its evolutionary purpose as a critical survival mechanism. He dives into how pain is transmitted through the nervous system, the different types of pain, and why different individuals perceive pain so differently. Sean shares insights into pain management strategies ranging from medications like NSAIDs and opioids to neuromodulation techniques such as transcutaneous electrical nerve stimulation (TENS). Additionally, this episode explores the interplay between sleep and chronic pain and the psychological and emotional dimensions of pain, and it includes a personal story from Peter about his own experience with pain and how Sean’s expertise helped him more than two decades ago.

We discuss:

• The definition of pain, and how our understanding of pain has evolved from a simplistic body-mind separation to a nuanced biopsychosocial model [2:30];
• The biological mechanisms behind how we perceive pain [9:30];
• The role of consciousness in the perception of pain, and how nociception functions during unconscious states [14:30];
• The four types of pain [22:00];
• Using fMRI to identify objective biomarkers of pain in the brain [31:30];
• The evolutionary role of pain in human behavior and survival [36:00];
• How the brain processes and modulates pain signals, Gate Control Theory, the variability in individuals’ pain perception, and effectiveness of neuromodulation techniques like TENS [41:00];
• The brain’s influence on pain: the role of emotion, beliefs, sleep, and individual differences in perception and tolerance [53:45];
• Peter’s personal journey with chronic back pain, and how the emotional consequences of pain can be more distressing than the pain itself [1:04:30];
• The pharmacology of common pain medications—NSAIDs, COX-2 inhibitors, and acetaminophen [1:09:30];
• Muscle relaxants: benefits, drawbacks, and personalized strategies [1:20:30];
• The definition of chronic pain [1:29:15];
• The role of antidepressants in pain management [1:30:15];
• Opioids: their controversial and nuanced role in pain management [1:33:45];
• Alternative therapies: acupuncture and cannabis [1:54:15];
• Fibromyalgia and chronic pain: clinical features, brain mechanisms, and emerging treatments like low-dose naltrexone [2:01:00];
• Possible brain benefits of low-dose naltrexone (LDN) for people with mild cognitive impairment [2:15:00];
• Peter’s recovery from severe chronic pain—how he went from immobility and high-dose opioids to full functionality [2:20:15];
• Breaking the pain cycle: how physical rehabilitation and psychological recovery work together in chronic pain treatment [2:30:45];
• Sean’s struggle with cluster headaches, and the value of knowledge, preparation, and empathy in both managing chronic pain and caring for patients [2:39:15]; and
• More.

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