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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.

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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.

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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.

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