The Peter Attia Drive

Steve Rosenberg is the Chief of Surgery at the National Cancer Institute, a position he has held continuously for the past 47 years. Steve is a pioneer in the field of immunotherapies for cancer and a recipient of nearly every major award in science. In this episode, Steve discusses his inspiration for devoting his career to cancer research and describes his keen observation of two cases of spontaneous cancer remission, driving him to learn how to harness the immune system to treat cancer. Steve's personal story essentially serves as a roadmap for the field of immunotherapy, from the very non-specific therapies such as interleukin-2, the discovery of tumor-infiltrating lymphocytes, checkpoint inhibitors, CAR T-cells, and adoptive cell therapy. Perhaps most importantly, Steve expresses his optimism for what lies ahead, especially in the face of some of the more recent discoveries with respect to tumor antigenicity. Finally, Steve discusses the human side of cancer which helps him to never lose sight of why he chose to become a physician. We discuss:

• Steve's childhood and inspiration to become a physician and medical researcher [3:15];
• Patients that influenced Steve's thinking about cancer and altered the course of his career [13:15];
• The discovery of antigen presentation, Steve's first job, and why he knew he wanted to study cancer [19:30];
• Cancer treatment in the early 1970's and Steve's intuition to utilize lymphocytes [26:45];
• Cancer cells versus non-cancer cells, and why metastatic cancer is so deadly [31:45];
• The problem with chemotherapy and promise of immunotherapy [38:30];
• How the immune system works and why it seems to allow cancer to proliferate [43:15];
• Steve discovers how to use interleukin-2 to mediate cancer regression [52:00];
• The immunogenic nature of certain cancers and the role of mutations in cancer [1:03:45];
• The improbable story of how CAR T cell therapy was developed [1:16:30];
• The discovery of tumor infiltrating lymphocytes (TIL) and engineering of T cells to recognize specific antigens [1:28:00];
• Steve's experience treating President Ronald Reagan's colon cancer [1:36:00];
• Why Steve has turned down many tempting job offers to focus on his research at the National Cancer Institute [1:41:00];
• The role of checkpoint inhibitors in cancer therapy and the promise of adoptive cell therapy [1:43:00];
• Optimism for using immunotherapy to cure all cancers [1:48:00];
• The human side of cancer and the important lessons Peter learned from working with Steve [1:52:15]; and
• More

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/StevenRosenberg

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

In this "Ask Me Anything" (AMA) episode, Peter and Bob discuss the longevity benefits from greater cardiorespiratory fitness (CRF) and greater muscle mass and strength. Conversely, they dive deep into the literature showing a rapid increase in morbidity and mortality risk as fitness levels decline with age. They also try to tease out the relative contributions of CRF, muscle mass, and strength. Additionally, they discuss the impact of fasting on muscle mass, the potential tradeoffs to consider, and finish by discussing why it's critical to maximize your fitness level. If you're not a subscriber and 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 on our website at the AMA #27 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:

• VO2 max and its association with cardiorespiratory fitness [2:45];
• Changing mortality risk based on VO2 max and cardiorespiratory fitness [7:45];
• The profound impact of improving cardiorespiratory fitness [15:15];
• Muscle mass, function, and loss with aging: how it's defined, measured, and the cutoff points for sarcopenia [25:00];
• Increasing mortality risk associated with declining muscle mass and strength [40:00];
• Muscle size vs. strength—which has the bigger impact on mortality risk? [58:00];
• Evaluating the cumulative impact of cardiorespiratory fitness and muscular strength on mortality risk when put together [1:03:30];
• Investigating the rising incidence in deaths from falls, and what role Alzheimer's disease might play [1:09:00];
• The impact of fasting on muscle mass and the potential tradeoffs to consider [1:14:30];
• The critical importance of working to maintain muscle mass and strength as we age [1:20:30]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/ama27/

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Matt Kaeberlein is globally recognized for his research on the biology of aging and is a previous guest on The Drive. In this episode, Matt defines aging, the relationship between aging, chronic inflammation, and the immune system, and talks extensively about the most exciting molecules for extending lifespan. He discusses the current state of the literature of testing rapamycin (and rapalogs) in animals and humans, including Matt's Dog Aging Project, and provides insights into how we can improve future trials by conceptualizing risk, choosing better endpoints, and working with regulators to approve such trials. He also examines the connection between aging and periodontal disease, biomarkers of aging, and epigenetic clocks. Finally, they explore some of the biological pathways involved in aging, including mTOR and its complexes, sirtuins, NAD, and NAD precursors. We discuss:

• The various definitions of aging [3:25];
• The relationship between disease and the biology of aging [16:15];
• Potential for lifespan extension when targeting diseases compared to targeting biological aging [22:45];
• Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules [32:45];
• Human studies using rapalogs for enhanced immune function [39:30];
• The role of inflammation in functional declines and diseases of aging [50:45];
• Study showing rapalogs may improve the immune response to a vaccine [56:15];
• Roadblocks to studying gero-protective molecules in humans [1:01:30];
• Potential benefits of rapamycin for age-related diseases—periodontal, reproductive function, and more [1:12:15];
• Debating the ideal length and frequency of rapamycin treatment for various indications like inflammation and longevity [1:21:30];
• Biomarkers of aging and epigenetic clocks [1:29:15];
• Prospects of a test that could calculate biological age [1:37:45];
• The Dog Aging Project testing rapamycin in pet dogs [1:42:30];
• The role of the mTOR complexes [1:58:30];
• mTor inhibitor called Torin2, mitochondrial disease and other potential pathways [2:09:45];
• Catalytic inhibitors, sirtuins, and NAD [2:19:15];
• NAD precursors: help or hype? [2:28:15]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/MattKaeberlein2

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Lawrence Wright is the author of The Looming Tower: Al-Qaeda and the Road to 9/11 which won the 2007 Pulitzer Prize for general nonfiction and was named one of Time's top 100 books of all time. In this episode, released just before the 20th anniversary of the September 11th attacks, Lawrence and Peter discuss the book and the lasting impact of that day. Lawrence reflects on his personal experiences on that day and how he was first drawn into reporting on the attacks. Lawrence then discusses in detail the history that led up to 9/11 which is really composed of two parallel stories. The first story is of the growing discontent in Muslim countries, the roots of Islamic radicalism, and how two extremists, Osama bin Laden and Ayman al-Zawahiri, joined forces to create the global terrorist organization Al-Qaeda. The second story is about how interpersonal and institutional conflicts between the FBI and CIA led to a massive failure in intelligence and resulted in multiple missed opportunities to predict and prevent the attacks on September 11th, 2001. Finally, they reflect on what we should have learned from 9/11 and the future of terrorism.

We discuss:

• Lawrence and Peter recount their personal experiences on September 11th, 2001 [3:30];
• How 9/11 changed the US into a security state and affected a generation [9:45];
• Lawrence's early coverage of 9/11 and how he knew it was going to be "the story of our lifetime" [14:45];
• Egyptian politics and the foundation of radical Islam [22:45];
• Anwar Sadat's presidency, assassination, and the birth of the radical Islamic movement [33:00];
• Aftermath of the Sadat assassination, and establishment of Al-Qaeda in Afghanistan [50:15];
• Osama bin Laden: Upbringing, involvement in the Soviet–Afghan War, and rise to celebrity status in Saudi Arabia [56:00];
• How the Western intervention in Saudi Arabia impacted Arab nationalist's hatred of America [1:15:30];
• Theorizing on the role of the religion in holding back Islamic states from making progress towards democracy [1:20:30];
• Bin Laden's time in Sudan [1:32:30];
• The CIA vs. the FBI: setting the stage for the failure of US intelligence [1:37:00];
• The mistake by US intelligence of not taking the bombings of the US embassies and the USS Cole seriously [1:46:00];
• Al-Qaeda in America: Losing the planners of the 9/11 attacks from our clutches and incompetence at the FBI and CIA [1:56:00];
• Problematic policies in Europe, and a direct message warning of the 9/11 attacks [2:14:45];
• The role of political infighting and personality conflicts that helped enable the 9/11 attacks and the lack of accountability [2:22:45];
• What came of the 9/11 commission, the role of the Saudi government, and the trials of Ali Soufan [2:36:00];
• Lessons from 9/11 and the future of terrorism [2:46:30]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/LawrenceWright

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

In this "Ask Me Anything" (AMA) episode, Peter and Bob answer numerous follow-up questions to recently discussed deep-dive topics such as the use of continuous glucose monitors and getting the most from zone 2 exercise. They also discuss the incredible feats of cyclists in the Tour de France through the lens of the amazing performance physiology required from these athletes. Additionally, Peter ties the conversation together by sharing his foundational framework when considering different interventions, even in the absence of data from a randomized controlled trial. If you're not a subscriber and 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 on our website at the AMA #26 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:

• Peter's foundational framework when considering different interventions [1:30];
• Applying Peter's framework to the idea of using a CGM [8:00];
• Why certain fruits have a bigger impact on glucose, and the limitations of a CGM can tell you [16:00];
• Importance of paying attention to insulin, and the prospects of a continuous monitor for insulin levels [20:00];
• How exercise impacts glucose and peak glucose numbers to stay under [24:15];
• Impact of anxiety on stress on glucose, and why it's important to calibrate your CGM [26:30];
• The five main tools for managing blood glucose numbers [33:45];
• Benefits of moving or exercising after a meal, and where ingested carbohydrates get can be stored [37:15];
• How to make decisions about an action or intervention in the absence of data from a rigorous, randomized controlled trial [40:30];
• The incredible athletic feats of Tour de France cyclists [48:30];
• Different modalities for doing zone 2 exercise: running, rowing, cycling, and more [1:00:15];
• Proxies for knowing your in zone 2 short of using a lactate monitor [1:07:30];
• Monitoring lactate for zone 2 exercise [1:10:00]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/ama26/

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Esther Perel is a psychotherapist and New York Times bestselling author who is an expert on modern relationships. In this episode, Esther describes how being a child of parents who narrowly survived the Holocaust shaped and influenced her perspectives and ultimately led to her to a career in therapy. She discusses how the generational differences in parenting, among other things, led to the rise of individualism with a focus on happiness and self-esteem to the detriment of our relationships and sense of community. Ultimately, the conversation focuses on the value of our relationships with others for one's sense of wellbeing, ability to deal with past trauma, resilience, and even our lifespan. She uses real world case studies to emphasize the therapeutic value of creating healthy relationships with others and oneself, explaining how our relationships with others can be a mirror into our own maladaptive behaviors. Esther explains how our self-narratives, which are often shaped by past trauma, may negatively impact our relationships with others and our emotional health, and emphasizes the value in trying to change them when warranted.

We discuss:

• Esther's background, adventures in hitchhiking, and how she ended up in the US [2:30];
• The lasting effects of the Holocaust on Esther's parents [8:45];
• Grappling with a dark past and feeling alive again after trauma [16:45];
• How Esther came to understand her parents in a new light [23:15];
• Why Esther chose therapy as her career [30:00];
• Using the concept of sexuality to understand society, culture, and people [40:00];
• The significance of sexual revolutions, and the similarities of medical advancements and advancements in psychotherapy [50:15];
• The impact of the rise of individualism and the focus on happiness and self-esteem [56:00];
• Generational differences in parenting and changing role of fathers [1:09:15];
• How our narratives affect our sense of wellbeing and relationships with others, and the challenge of changing them [1:17:15];
• Generational effects of past trauma, and how relationship to others can be a mirror into your maladaptive behavior [1:30:30];
• The role of willpower in one's ability change their behavior and improve their relationships [1:40:00];
• How your relationships impact longevity and the importance of being capable of sitting in uncomfortable emotions [1:43:45];
• Esther's definition of resilience and the dangers of believing everything you think or feel [1:50:00];
• Questions about the human condition that Esther wants to explore [1:57:30]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/EstherPerel

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Steve Austad is a distinguished professor of biology at the University of Alabama and director of one of the Nathan Shock Centers of Excellence in aging biology. Steve's current research seeks to understand the underlying causes of aging, specifically with a long-term goal of developing medical interventions that slow the age-related decay of human health. In this episode, Steve tells Peter about his unusual childhood and stints as a cab driver and lion tamer. He goes on to describe what led to his focus on studying aging and some of the major challenges and limitations of working with laboratory animals. Steve and Peter talk about the relationship between caloric restriction and lifespan, including some of the most important studies exploring this question. Additionally, they hypothesize what might explain the sex-related differences in longevity between men and women, explain the importance of finding longevity biomarkers, and discuss the most promising molecules as potential longevity agents. We discuss:

• Steve's background and unusual childhood [2:30];
• Steve's adventures driving a cab in New York City [9:00];
• How Steve drove to LA and accidentally became a lion tamer [13:30];
• How Steve's early graduate school experiences led him to study longevity [23:00];
• The challenges and limitations of working with lab mice [30:45];
• The connection between caloric restriction and lifespan [43:00];
• Mice vs. rats and rodent aging experiments [51:15];
• The impact of dietary composition and the harm of sucrose: Comparing two caloric-restriction studies in monkeys [56:00];
• Challenges of studying animals due to major differences in the lab animal vs. wild animals [1:10:00];
• Human studies of calorie restriction [1:24:45];
• Better dietary protocols for humans: Alternatives to long-term caloric restriction [1:33:45];
• The protective effect of fasting [1:38:00];
• Reflecting on the sex differences in human lifespan, and why women have more neurodegenerative diseases [1:45:45];
• The importance of identifying longevity biomarkers and which ones show the potential to change the landscape of longevity research [2:03:30];
• Molecules showing the most promise as longevity agents [2:14:00]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/SteveAustad

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

In this "Ask Me Anything" (AMA) episode, Peter and Bob dive deep into cancer screening, including why it's important, what you need to know about a test, and Peter's approach with patients. They specifically discuss various screening methods, explain important terms like sensitivity and specificity, and how layering and stacking different tests in tandem can improve predictive values. They conclude with a discussion on one of the more exciting screening tools, diffusion-weighted MRI, and how it's changing the cancer screening landscape. If you're not a subscriber and 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 on our website at the AMA #25 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:

• The importance of cancer screening [1:15];
• Cancer screening terms: sensitivity, specificity, false positives, and false negatives [8:25];
• Cancer screening terms: positive and negative predictive value [17:00];
• Improving predictive value by layering tests, and the predictive values of mammograms [25:45];
• How smoking impacts the predictive value of cancer screening [30:45];
• Liquid biopsies for ruling out cancer and the blind spots of common cancer screening tests [33:00];
• The difference between cancer originating from inside versus outside the body [41:15];
• How diffusion-weighted MRI is changing cancer screening [45:15];
• Summary of Peter's approach to cancer screening [53:45]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/ama25

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Katherine Eban is an award-winning investigative journalist who previously appeared on The Drive to discuss the widespread fraud in the generic drug industry. In this episode, she discusses the content of her recent Vanity Fair article, which examined the evidence for the theory that the COVID-19 pandemic resulted from a virus lab escape as opposed to a natural virus that came from an animal host. Katherine and Peter walk through the evidence for both theories as well as discuss the long and troubling history of dangerous lab leaks and safety concerns about the Wuhan Institute of Virology. They also talk about the controversy surrounding gain-of-function research and its funding by the US government. Finally, they conclude with a discussion on the likelihood of definitively establishing the origins of the virus given the Chinese government's lack of cooperation and highlight the fact that the many barriers to performing a full investigation may be the most troubling aspect of the controversy. This episode was originally recorded on July 6, 2021.

We discuss:

• An overview of the lab leak controversy [1:30];
• The troubling history of lab leaks of dangerous pathogens [8:30];
• The zoonotic transmission theory: did SARS2 come from a bat? [11:45];
• The debate about gain-of-function (GoF) research [26:15];
• Questions about US funding of GoF research in China [33:45];
• The uncertain significance of the furin cleavage site [51:30];
• Discerning what's most important about both the zoonotic transmission and lab leak theories [1:01:15];
• Barriers to a full investigation [1:19:15]; and
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/katherineeban2

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.

Hugh Jackman is an award-winning actor and an overall fascinating and introspective individual. In this episode, Hugh reflects upon his acting career, including how he navigated many tough decisions that led to important professional turning points for him. Peter and Hugh have an intimate discussion related to handling professional criticism, self-identity, spirituality, raising kids, and the role that past trauma often plays in extremely driven individuals. Hugh gives the inside scoop on some of his most well-known character roles and explains how he finds the energy to consistently perform. Finally, they tie the conversation together with a discussion on the importance of physical and mental health and wellbeing. We discuss:

• Hugh's voracious curiosity and early years of his acting career [2:15];
• Self-identity, overworking, and the importance of living well [9:15];
• Handling criticism and letting go of the desire to please everyone [18:30];
• Dismissing vitriol on social media, and the challenge of communicating science [28:15];
• Going with your gut and the value in finding the right partner [31:30];
• A hard decision that lead to a turning point in Hugh's life [40:15];
• How driven personalities often develop from a place of trauma, and how to avoid going from productive to destructive [47:00];
• The effect of fame on Hugh's family [58:45];
• How Hugh finds the energy to consistently perform, and the spiritual connection he feels when acting [1:07:15];
• Hugh's experiences on the set of The Fountain and the meaning behind the film [1:26:30];
• The potential of imagination, the idea of a higher power, and thoughts on science vs. religion [1:33:45];
• The deep connection Hugh felt to Logan (his character in Wolverine) [1:41:45];
• Reflections on physical aging, emotional wellbeing, and longevity [1:55:15]; and
• More

Learn more: https://peterattiamd.com/

Show notes page for this episode: https://peterattiamd.com/HughJackman

Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/

Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/

Connect with Peter on Facebook | Twitter | Instagram.