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Ted Schaeffer is an internationally recognized urologist specializing in prostate cancer and a returning guest on The Drive. In this episode, Ted provides insights into the role testosterone plays, or doesn't play, in the initiation and progression of prostate cancer. He unpacks the findings and limitations of the recent TRAVERSE trial, exploring the complex relationship between testosterone and prostate cancer. Ted delves into the molecular nature of prostate cancer, explaining the androgen receptor saturation theory and the potential impact of testosterone on cancer growth. He also discusses the use of the Decipher test to predict cancer aggressiveness and guide targeted treatment. Furthermore, Ted shares how he counsels patients regarding testosterone replacement therapy (TRT), including its safe administration in patients with low-grade prostate cancer. Additionally, he highlights advancements in prostate cancer therapies and biomarkers that help develop precise treatment strategies while minimizing the need for broad androgen deprivation therapy.

We discuss:

• Background on the TRAVERSE trial: insights into exogenous testosterone and prostate cancer risk [3:00];
• The androgen receptor saturation theory: how different organs respond to varying levels of testosterone [10:30];
• The relationship between testosterone levels and prostate cancer aggressiveness: how aggressive prostate tumors have lower androgen receptor activity and rely on different growth mechanisms [16:15];
• Using the Decipher score to assess prostate cancer aggressiveness and guide personalized treatment strategies [23:45];
• Considerations for testosterone replacement therapy: how Ted counsels patients, how TRT can be safely administered in patients with low-grade prostate cancer, and more [31:15];
• Advancements in prostate cancer therapies and PSA as a biomarker for precise treatment decisions, minimizing the need for broad androgen deprivation therapy [38:30]; and
• More.

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Isaac "Zak" Kohane, a pioneering physician-scientist and chair of the Department of Biomedical Informatics at Harvard Medical School, has authored numerous papers and influential books on artificial intelligence (AI), including The AI Revolution in Medicine: GPT-4 and Beyond. In this episode, Zak explores the evolution of AI, from its early iterations to the current third generation, illuminating how it is transforming medicine today and unlocking astonishing possibilities for the future. He shares insights from his unconventional journey and early interactions with GPT-4, highlighting significant AI advancements in image-based medical specialties, early disease diagnosis, and the potential for autonomous robotic surgery. He also delves into the ethical concerns and regulatory challenges of AI, its potential to augment clinicians, and the broader implications of AI achieving human-like creativity and expertise.

We discuss:

• Zak’s unconventional journey to becoming a pioneering physician-scientist, and his early interactions with GPT-4 [2:15];
• The evolution of AI from the earliest versions to today’s neural networks, and the shifting definitions of intelligence over time [8:00];
• How vast data sets, advanced neural networks, and powerful GPU technology have driven AI from its early limitations to achieving remarkable successes in medicine and other fields [19:00];
• An AI breakthrough in medicine: the ability to accurately recognize retinopathy [29:00];
• Third generation AI: how improvements in natural language processing significantly advanced AI capabilities [32:00];
• AI concerns and regulation: misuse by individuals, military applications, displacement of jobs, and potential existential concerns [37:30];
• How AI is enhancing image-based medical specialties like radiology [49:15];
• The use of AI by patients and doctors [55:45];
• The potential for AI to augment clinicians and address physician shortages [1:02:45];
• The potential for AI to revolutionize early diagnosis and prediction of diseases: Alzheimer’s disease, CVD, autism, and more [1:08:00];
• The future of AI in healthcare: integration of patient data, improved diagnostics, and the challenges of data accessibility and regulatory compliance [1:17:00];
• The future of autonomous robotic surgery [1:25:00];
• AI and the future of mental health care [1:31:30];
• How AI may transform and disrupt the medical industry: new business models and potential resistance from established medical institutions [1:34:45];
• Potential positive and negative impacts of AI outside of medicine over the next decade [1:38:30];
• The implications of AI achieving a level of creativity and expertise comparable to exceptional human talents [1:42:00];
• Digital immortality and legacy: the potential to emulate an individual's personality and responses and the ethical questions surrounding it [1:45:45];
• Parting thoughts [1:50:15]; and
• More.

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Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU.

We discuss:

• The amazing potential of cyclist Tadej Pogačar [2:00];
• Metrics for assessing athletic performance in cyclists and how that impacts race strategy [7:30];
• The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [16:15];
• Tadej Pogačar’s race strategy and mindset at the Tour de France [23:15];
• Defining Zone 2, fat oxidation, and how they are measured [26:00];
• Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:00];
• Lactate levels and fat oxidation as it relates to Zone 2 exercise [39:15];
• How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:00];
• Bioenergetics of the cell and what is different in elite athletes [56:30];
• How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:07:45];
• Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:14:15];
• How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:20:15];
• Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:24:00];
• Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:40:30];
• How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:50:30];
• Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:00];
• The effects of metformin, NAD, and supplements on mitochondrial function [2:04:30];
• The role of lactate and exercise in cancer [2:12:45];
• How assessing metabolic parameters in long COVID patients provides insights into this disease [2:18:30];
• The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:00];
• Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:00];
• Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:38:30]; and
• More.

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