#323 - CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this special episode of The Drive, Peter tackles a wide range of listener questions submitted over the past year. The discussion spans essential topics such as exercise—covering grip strength, traveling workouts, and why Peter doesn’t consider exercise an ideal weight-loss strategy—and the top biomarkers everyone should track. He also explores promising new longevity research, his evolving views on longevity, and frameworks like “objective, strategy, tactics” for personalized decision-making. The episode wraps up with insights on building good habits and a glimpse into Peter’s recent reading list. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the Special AMA show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of episode topics (and Peter’s car stereo saga) [1:45]; The importance of grip strength and the best methods for training it effectively [3:45]; Exercise while traveling: strategies for staying active and maintaining an exercise routine [14:45]; Why women should prioritize strength training [18:00]; The limited role of exercise in weight loss and its greater importance in improving health, body composition, and insulin sensitivity [19:45]; The “top five most important biomarkers” for assessing health [22:45]; Promising developments in longevity research [28:15]; The development of Klotho as a neuroprotective drug: challenges, timelines of trials, and more [34:00]; Peter’s updated view on the potential of epigenome manipulation to restore aged cells to their youthful state [39:45]; How reversing age-related epigenetic changes in immune cells could revolutionize our approach to aging and disease [43:30]; The “objective, strategy, tactics” framework, and the importance prioritizing impactful lifestyle habits over less significant health trends [49:30]; Strategies for building and maintaining good habits [56:45]; How to think about drugs and supplements as part of a longevity toolkit [1:02:00]; Peter’s recent reading list [1:05:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this "Ask Me Anything" (AMA) episode, Peter dives deep into one of the most frequently discussed and often misunderstood topics: nutrition. From weight loss and maintenance to the intricate relationship between nutrition and exercise and body composition, Peter addresses the complexities of nutrition research and explores the perennial question of whether there is a "best diet." He provides practical insights on how to choose the right diet for your unique needs, discusses the role of protein and processed foods, and outlines the key questions to help you optimize your approach to eating. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #66 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The key nutrition-related topics to be discussed [1:30]; Why Peter is not fond of discussing nutrition: limitations of nutrition research, the pitfalls of extreme certainty in dietary discussions, and the body's adaptability to varied diets [3:30]; Key health metrics to monitor to evaluate the effects of nutrition [9:30]; The relationship between nutrition and exercise as they relate to weight loss, maintenance, and gain [12:30]; How increased muscle mass from resistance training impacts calorie burn, body composition, glucose metabolism, and overall health benefits [19:45]; Comparing the impact of fitness and nutrition on lifespan and healthspan: data showing fitness to be a more significant predictor of mortality than nutrition [23:30]; The myth of a “best diet,” factors that determine the effectiveness of a diet, and data suggesting benefits of the Mediterranean diet [39:00]; How long to trial a new diet, the importance of measurable goals, and the appropriate timescales for observing meaningful changes [48:30]; The inherent challenges in nutrition research: variability in dietary exposures, limitations in study design, the body’s adaptive nature which dampen the effects, and more [51:15]; Nutritional approaches for chronic diseases like cardiovascular disease and type 2 diabetes [58:45]; Emerging studies on dietary interventions for non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) [1:02:45]; Practical considerations for individuals to identify the best diet for them: protein intake, energy balance, macronutrient adjustments, and micronutrient levels [1:06:00]; Understanding processed vs. ultra-processed foods [1:09:15]; The effects of ultra-processed foods on health [1:12:30]; Questions that someone should ask themselves if they’re looking to fine-tune their diet [1:18:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Dr. Saum Sutaria is the Chairman and CEO of Tenet Healthcare and a former leader in McKinsey & Company’s Healthcare and Private Equity Practices, where he spent almost two decades shaping the field. In this episode, Saum unpacks the complexities of the U.S. healthcare system, providing a detailed overview of its structure, financial flows, and historical evolution. They delve into topics such as private insurance, Medicare, Medicaid, employer-sponsored coverage, drug pricing, PBMs and the administrative burdens impacting the system. Saum’s insights help connect healthcare spending to broader economic issues while exploring potential reforms and the role of technology in improving efficiency. Saum highlights how choice and innovation distinguish the U.S. healthcare system, explores the reasons behind exorbitant drug prices, and examines the potential solutions, challenges, and trade-offs involved in lowering costs while striving to improve access, quality, and affordability. The opinions expressed by Saum in this episode are his own and do not represent the views of his employer. We discuss: The US healthcare system: financial scale, integration with economy, and unique challenges [5:00]; Overview of how the US healthcare system currently works and how we got here [9:45]; The huge growth and price impact due to the transition from out-of-pocket payments in the 1950s to the modern, third-party payer model [18:30]; The unique structure and challenges of the US healthcare system compared to other developed nations [22:00]; Overview of Medicare and Medicaid: who they cover, purpose, and impact on healthcare spending [27:45]; Why the US kept a employer-sponsored insurance system rather than pursue universal healthcare [32:00]; The evolution of healthcare insurance: from catastrophic coverage to chronic disease management [36:00]; The challenge of managing healthcare costs while expanding access and meeting increased demand for chronic illness care [44:15]; Balancing cost, choice, and access: how the US healthcare system compares to Canada [48:45]; The role of the US in pharmaceutical innovation, it’s impact on drug pricing, and the potential effects of price controls on innovation and healthcare costs [56:15]; How misaligned incentives have driven up drug prices in the US [1:05:00]; The cost of innovation and choice, and the sustainability of the current healthcare cost expenditures in the US in the face of a shrinking workforce and aging population [1:11:30]; Health outcomes: why life expectancy is lower in the US despite excelling at extending lifespan beyond 70 [1:18:45]; Potential solutions and challenges to controlling drugs costs in the US while balancing choice and access and preserving innovation [1:26:15]; Balancing GLP-1 drug innovation with affordability and healthcare spending sustainability [1:40:00]; Reducing healthcare spending: complexities, trade offs, and implications of making needed cuts to healthcare expenditures [1:46:45]; The role of government regulation, opportunities for cost savings, and more [1:56:15]; Hospital billing: costs, charges, complexities, and paths to simplification [2:01:15]; How prioritizing access and choice increased expenditures: reviewing the impact of healthcare exchanges and the Affordable Care Act [2:08:00]; Feasibility of a universal Medicare program, and what a real path to sustainable healthcare looks like [2:15:45]; The challenge of long-term care and the potential of innovation, like device-based therapies and AI, to improve health [2:23:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Bill Perkins is one of the world’s most successful hedge fund managers and entrepreneurs, and the author of the bestseller, Die With Zero. In this episode, Bill unpacks the Die With Zero philosophy which challenges conventional thinking related to the balance between health, wealth, and time—the three variables important for fulfillment. Bill makes the case that we should strive for maximum net fulfillment rather than net worth (or even health). He argues that we need to optimize our life to have memorable experiences before it’s too late and that most people are over-saving and under-living. Bill also explains how one can apply the principles in Die With Zero to break out of “autopilot” and optimize their life to achieve maximum net fulfillment. We discuss: Bill’s upbringing, background, and first job on Wall Street [2:45]; A missed experience and feeling of regret that shaped Bill’s thinking [13:45]; Thinking in terms of time, and the relationship between money, time, and health [16:30]; Solving for net fulfillment and allocating your time based on the seasons of life [26:45]; How Bill thinks about risk, opportunity costs, and the difference between fear and risk tolerance [35:00]; Optimizing for fulfillment, finding purpose outside of work, and more [41:15]; Thinking about the order of experiences you want to have based on seasons of life [49:30]; Bill’s unique perspective on philanthropy and a more impactful way to give money away [54:15]; Applying the principles in ‘Die With Zero’ to maximize fulfillment [1:03:30]; How to break out of living life on autopilot [1:13:45]; When should your net worth peak? [1:17:30]; Taking calculated risks [1:21:00]; Bill shares a lesson from his incredible birthday [1:24:45]; How Bill’s philosophy has evolved since writing Die With Zero [1:33:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter dives into the world of red light therapy in response to frequent questions from listeners. Peter provides a comprehensive exploration, starting with the basics of red light therapy and why it’s getting so much attention. The conversation examines the latest data on various applications, including aging, skin health, acne, wound healing, hair loss, eye health, exercise performance, metabolic health, weight loss, inflammation, injury recovery, and menstrual cramps. Peter analyzes the scientific literature on each use case and concludes with a summary table that provides an easy-to-follow breakdown of the potential benefits of red light therapy across these areas. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #65 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of topics and the motivation behind exploring red light therapy [1:45]; The basic science of red light therapy [3:15]; The unique penetration properties of red light [6:00]; What happens when tissue is exposed to red light [9:30]; Exploring red light therapy’s potential to combat aging [11:00]; Red light therapy for treating acne [13:00]; Red light therapy for aiding in wound healing [18:45]; Red light therapy for hair loss: promising benefits and practical advice [24:15]; Analyzing the evidence of a positive or negative effect of red light therapy on the eyes [28:00]; Red light therapy’s impact on performance and recovery [30:30]; Red light therapy’s impact on metabolic health: analyzing the limited evidence for improved glucose metabolism [32:45]; Red light therapy for weight loss and targeted fat reduction [36:45]; Red light therapy for inflammation, chronic pain, and injury rehabilitation [41:00]; Red light therapy as a treatment for menstrual cramps [43:45]; Summary: promising applications of red light therapy, unsupported claims, and costs to consider [46:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions on diverse topics such as dopamine and addiction with Anna Lembke, the current state and exciting future of CRISPR-mediated gene editing with Feng Zhang, how to build and maintain strong bones from youth to old age with Belinda Beck, how calorie restriction may influence longevity and metabolic health with Eric Ravussin, and the role of testosterone and TRT in prostate cancer with Ted Schaeffer. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #325 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of topics to be covered [1:45]; Anna Lembke episode: addiction, dopamine's role in pleasure and pain, and managing addictive behaviors [4:15]; Follow-up questions about addiction: heritability, cold therapy, exercise, and strategies for breaking addictive behaviors [14:45]; Feng Zhang episode: the potential of gene editing with CRISPR technology for treating diseases, and the challenges ahead [21:00]; Feng Zhang’s impactful education experience, and how early exposure and curiosity-driven learning can develop scientific interest for kids [28:30]; The future of CRISPR: weighing the scientific potential to combat complex diseases against ethical considerations around genetic modification [33:45]; Belinda Beck episode: how to build and maintain strong bones from youth to old age [37:30]; How both nutrition and exercise are crucial for bone health at all ages, and why it’s never too late to start [54:45]; Eric Ravussin episode: calorie restriction, energy expenditure, exercise for weight maintenance, and more [59:00]; Measuring energy intake and energy expenditure: techniques and challenges [1:09:45]; ed Schaeffer episode: the nuance role of testosterone in prostate cancer, TRT, and the need for better cancer biomarkers [1:14:30]; Peter’s favorite bands [1:25:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Eric Ravussin is a world-renowned expert on obesity, metabolism, and aging whose pioneering research has shaped much of what we understand today about energy balance and caloric restriction. In this episode, Eric shares insights from his cutting-edge work on energy expenditure—a critical factor in understanding how our bodies regulate weight and appetite. He discusses methods for measuring energy output, energy balance, food intake, and appetite regulation, and explores key studies on macronutrient manipulation. Eric then delves into the CALERIE study on caloric restriction, highlighting insights related to biomarkers of both primary and secondary aging. The conversation also covers the potential of GLP-1 agonists to replicate these effects and looks ahead to how AI and technology could transform metabolic research in the coming years. We discuss: Eric’s background and current work metabolism and measuring energy expenditure [3:00]; The science behind metabolic chambers for measuring energy expenditure, and the complexities of indirect and direct calorimetry [8:00]; The body's regulatory systems for maintaining energy balance and the primary influence of energy intake on body weight [18:30]; The epidemic of obesity and a discussion of resting metabolic rate [24:45]; The impact of exercise, appetite, gut hormones, and eating patterns on weight regulation [28:45]; Experiments looking at how macronutrient composition affects energy expenditure [38:45]; The challenges of studying diet in real-life settings, the potential of personalized nutrition, and how public health policy could play a role in guiding nutritional habits [51:00]; The importance of protein in the diet, the limitations of dietary data collection, and how AI could potentially transform nutrition science [1:08:15]; How Eric’s interest in caloric restriction (CR) began with Biosphere 2, metabolic efficiency's role in aging, and goals of the CALERIE study [1:15:15]; The CALERIE study: exploring the real-world impact of caloric restriction [1:28:00]; Notable findings from the CALERIE study after two years: sustained weight loss, participant retention, and more [1:40:00]; The effect of caloric restriction on the hallmarks of aging [1:47:00]; The challenge of applying CR to the general population, the potential of drugs and exercise to mimic the effects of CR [1:55:45]; Upcoming study comparing caloric restriction to time-restricting eating, and Peter’s takeaways from the discussion [2:02:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng’s personal journey, the impact of mentorship, and the future potential of genetic medicine. We discuss: Feng’s background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45]; The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45]; How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00]; The limitations of earlier gene-editing technologies prior to CRISPR [28:15]; How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45]; CRISPR’s potential in treating genetic diseases and the challenges of effective delivery [48:00]; How CRISPR is used to treat sickle cell anemia [53:15]; Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15]; How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45]; Advantages of Cas13’s ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00]; CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45]; The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45]; Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45]; Feng’s early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00]; Feng’s optimism about the trajectory of science [1:58:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Belinda Beck, founder of The Bone Clinic and a leading authority on exercise physiology and bone health, delves into the science of osteoporosis, bone density, and the lifelong importance of maintaining skeletal health. In this episode, she explains how the foundation for strong bones is established during childhood, offering valuable advice for parents on optimizing bone health for their kids. She also explores how bone remodeling occurs throughout life, driven by activity, nutrition, and hormones. Belinda highlights the power of resistance training in improving bone strength, even for those at risk of bone loss, and emphasizes the role of essential vitamins and minerals in maintaining bone health. She shares practical strategies, backed by research, for preventing fractures and combating osteoporosis. We discuss: Belinda’s journey into bone health research and training [2:45]; The physiology of bone and how bones adapt to mechanical loading [8:15]; Bone development from birth to adulthood, why early life is a crucial period, the functions of osteoblasts and osteoclasts, and gender differences in BMD [14:00]; How parents can optimize their children’s bone health through diet (calcium and vitamin D), sunlight exposure, and physical activity [27:30]; The best sports and activities for promoting bone health, weight training for kids, and advice for parents [36:30]; The impact of corticosteroid use on bone health in children and strategies to minimize negative effects [48:30]; Advice for people in middle age to preserve bone density: physical activity and bone-loading exercises [52:00]; Bone loss during the menopause transition for women: hormone replacement therapy and other strategies to mitigate BMD losses [59:30]; Interpreting the bone mineral density results from a DEXA scan: T-score, Z-score, and more [1:03:00]; The LIFTMOR study: testing the effects of heavy weightlifting on bone health in postmenopausal women with low bone density [1:10:15]; Profound benefits of weight training outside of BMD improvements: exploring the broader impacts on patients in the LIFTMOR study [1:19:30]; Guidance for people wanting to use exercise designed to improve their bone health [1:29:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Anna Lembke is the Chief of the Stanford Addiction Medicine Dual Diagnosis Clinic and author of Dopamine Nation: Finding Balance in the Age of Indulgence. In this episode, Anna dives deep into the biochemistry and neurobiology of addiction, exploring the critical role of dopamine and the prefrontal cortex. She shares her framework for diagnosing and treating addiction, providing real-world examples involving alcohol, gambling, cannabis, social media, and more. Anna outlines the risk factors for addiction, including inherited and nurture-based risks, explores the rise of addictions in younger generations, and discusses effective ways to address these issues with children. Additionally, she touches on healthy coping strategies, the evolution of the “marshmallow experiment,” and provides insights into GLP-1 agonists as a possible tool for addiction treatment. Finally, she reflects on the value of 12-step programs and how she navigates the emotional challenges of her work. We discuss: The role of dopamine and the prefrontal cortex in addiction [3:00]; The clinical definition of addiction and the behavioral criteria for diagnosing it [13:00]; Assessing alcohol use: patterns, risks, and addiction diagnosis [17:15]; Applying the addiction diagnosis framework using gambling as an example [21:45]; Exploring addiction variability: how nature, nurture, and access shape individual vulnerability and drug of choice [25:15]; How abstinence from addictive behaviors can help reset the brain’s reward system and improve mental health [41:15]; Safely abstaining from addiction substances, drugs needing medical supervision, and other key considerations [51:30]; Transitioning from abstinence to long-term recovery: tools and considerations [59:00]; Exploring behavioral addictions like sex addiction, and the gender differences in addiction patterns [1:08:30]; Factors contributing to the increasing levels of addiction across the world [1:13:45]; How online pornography can affect young boys' developing brains and lead to addictive behaviors, and strategies for parents to address this issue [1:23:30]; The link between social media use and declines in mental health, potential solutions, and protective measures [1:34:45]; How exercise affects brain chemistry, the role of dopamine and endorphins, and how exercise can become addictive [1:44:00]; Cold-water immersion for mood regulation, and other healthy coping strategies [1:47:15]; The “marshmallow experiment”: how broken promises affect behavior and trustworthy environments help children develop self-control [1:54:00]; Can GLP-1 agonists be useful in treating addiction? [1:58:30]; The benefits of 12-step programs [2:06:00]; Why understanding a patient’s story is essential for meaningful psychiatric care [2:11:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube