#62 - Keith Flaherty, M.D.: Deep dive into cancer—History of oncology, novel approaches to treatment, and the exciting and hopeful future
In this episode, Keith Flaherty, director of clinical research and targeted cancer therapy at Massachusetts General Hospital, shares his vast wealth of knowledge in cancer starting with the history of treatment from chemotherapy to radiation to surgical therapy and where those methodologies seemed to have leveled off. He also walks us through the timeline of advancements (and lack there of) from when the War on Cancer was declared in the 1970s, through the sequencing of the entire human genome, and all the way to today. Keith dives into the topic of immunotherapy, probably the most exciting recent development in cancer therapy, and also provides us a rundown of his notion of a different approach to cancer that attacks all the essential pillars of cancer growth and survival. Finally, we talk a little bit about liquid biopsies, we discuss the roles of CRISPR and other potentially over-hyped therapies with respect to cancer. We also touch on stem cell therapy a bit, as well as some other common cancer-related questions such as the role of vitamin D and sun exposure in melanoma, and much more. We discuss: Growing up around medicine, and finding a career that you love [7:30]; Medicine as a career, limitations of the med school teaching approach, and the dynamic and accelerating field of medicine and technology [16:30]; Explaining chemotherapy, radiation, and how a cancer develops [23:45]; Surgical oncology, cure rate of solid tumors, and survival rate after tumor removal [33:15]; 25 years after the War on Cancer is declared, gene sequencing, and why Keith’s was fascinated by the HIV case study [37:15]; Cancer immunotherapy: History, how it works, and why some cancers respond and others don’t [46:00]; MHC complexes, and cancer cloaking mechanisms [56:00]; Comparative biology of cancer: Why some cancer can evade immune detection better than others [1:03:00]; What we learned from the Cancer Genome Atlas Project [1:07:00]; Defining targeted therapy, HER2 breast cancer, chronic leukemia, and the translocation of chromosomes [1:12:00]; Tumor protein P53, the most famous tumor suppressor gene and its ubiquity in cancer [1:17:45]; Activated oncogenes, the RAS pathway, PI3 kinase, RAF gene, and Keith’s “aha moment” [1:24:15]; Advice for starting your career as a scientist/clinician [1:37:00]; Fusion-driven cancers, targeted therapy, and the Bcr-Abl/chronic myelogenous leukemia case study [1:39:45]; Targeted therapy for fusion-driven solid tumors, adjuvant systemic therapy, and the HER2 breast cancer example [1:53:00]; Advancing melanoma treatment, survival, and cure rates with BRAF-MEK combo therapy [1:59:15]; The fundamental pillars of cancer growth and survival, and the toolkit we need to attack cancer from all angles [2:02:40]; Peter’s clinical framework for thinking about cancer and how Keith might improve it, and how the biotech environment is hampering our ability to put together novel cancer treatments [2:05:00]; How useful is CRISPR in terms of tumor suppressing? [2:16:15]; Liquid biopsies as a therapeutic monitoring tool [2:18:00]; Stem cell therapy: The efficacy and potential risks [2:25:15]; Aging and cancer: Is cancer inevitable? [2:28:45]; Vitamin D supplements, sun exposure, melanoma, and exercise [2:32:30]; How and why Keith has straddled the line between science/research and industry/drug companies, and the importance of getting more voices of practitioners at the table [2:42:00]; and More. Learn more at .
#61 - Rajpaul Attariwala, M.D., Ph.D.: Cancer screening with full-body MRI scans and a seminar on the field of radiology
In this episode, radiologist/engineer, Raj Attariwala, explains how he was able to apply his engineering background to create a unique MRI scanner that is capable of constructing whole-body images with a resolution that is unmatched in the industry. Peter and Raj discuss the implications of such a robust, radiation-free imaging tool on the early detection of cancer. They dive deep into cancer screening and define terms such as sensitivity and specificity that are necessary to really understand this complex space. They then describe the biggest risks involved in this type of screening (false positives) and how Raj’s unique technology and process might drive down this risk substantially. But before that, they discuss all the common imaging technology from X-ray, to CT scan, to PET scans, to ultrasound, to MRI, and more. They touch on the history of each, how they work, the usefulness and limitations of each of them, as well as the varying risks involved such as radiation exposure. If you are interested in cancer screening and/or you’ve ever wondered how any radiology tool works, this episode is for you. We discuss: Raj’s road from engineering to radiology [7:45]; How X-ray works, the risk of radiation exposure, and the varying amounts of radiation associated with the different imaging technologies [18:00]; Computed tomography scans (CT scans): The history of CT, how it works, and why we use contrast [27:45]; Ultrasound: Benefits and limitations, and a special use for the heart [40:45]; Detecting breast cancer with mammography: When is works, when you need more testing, and defining ‘sensitivity’ and ‘specificity’ [51:15]; Magnetic resonance imaging (MRI): How it works, defining terms, and looking at the most common types of MRI [1:03:45]; Brain aneurysms: Using MRI to find them and save lives [1:23:45]; Raj’s unique MRI technology [1:30:00]; The risk of false positives in cancer detection, and how Raj’s MRI can reduce the number of false positives (i.e., increase specificity) [1:43:40]; The unique software Raj created to pair with his MRI machine [1:51:15]; Comparing the radiation exposure of a whole-body PET-CT to Raj’s equipment (DWIBS-MRI) [1:53:40]; How diffusion-weighted magnetic resonance imaging (DW-MRI) has revolutionized cancer screening [1:55:15]; Why a DW-MRI is still not a perfect test [1:59:00]; The potential for advancing MRI technology: Where does Raj think it could improve in the next 5-10 years? [2:03:00]; Are there any commercially available scanners that can match the resolution of Raj’s images? [2:06:00]; Machine learning: When and where might machine learning/AI impact the field of radiology? [2:08:40]; and More. Learn more at .
The one-year anniversary episode with Olivia Attia: Reflecting on the past year and looking forward to exciting times ahead
In this anniversary episode, Olivia, Peter's daughter who initially kicked off The Drive podcast with her sneak peek episode, returns to ask Peter the tough questions on how the podcast is going, what he has learned along the way (and how he plans to make it better), what exciting things are in store for the future, and plenty more.
#60 - Annie Duke, decision strategist: Poker as a model system for life—how to improve decision making, use frameworks for learning, and apply ‘backcasting’ to boost your odds for future success
In this episode, former World Series of Poker champion and author, Annie Duke, explains how poker is a pertinent model system for decision making in the real world, a system which blends imperfect information with some unknown percentage of both luck and skill. We go through the decision-making matrix, and how we spend most of our energy focusing on just one of the four quadrants at the expense of the learning opportunities that come from the other 75% of situations. Annie also shares how this evaluation of only the bad outcomes (and our tendency to judge others more harshly than ourselves in the face of a non-status quo decision), leads individuals, leaders, and teams to avoid bad outcomes at all costs. This avoidance is at the cost of the types of decisions which lead to progress and innovation both personally, and societally, across many realms from poker to sports to business to medicine. We also dive deep into a framework for learning, and the levels of thought required to rise to the top of a given domain. Finally, we talk about something that resonated deeply with me in terms of how I think about extending healthspan, which is the concept of “backcasting”. We discuss: Annie’s background, favorite sports teams, and Peter’s affinity for Belichick [7:30]; Chess vs. poker: Which is a better metaphor for decision making in life (and medicine)? [12:30]; Thinking probabilistically: Why we aren’t wired that way, and how you can improve it for better decision making [18:15]; Variable reinforcement: The psychological draw of poker that keeps people playing [25:15]; The role of luck and skill in poker (and other sports), and the difference between looking at the short run vs. long run [38:00]; A brief explanation of Texas hold ‘em [47:00]; The added complexity of reading the behavior of others players in poker [53:15]; Why Annie likes to “quit fast”, and why poker is still popular despite the power of loss aversion [58:30]; Limit vs. no limit poker, and how the game has changed with growing popularity [1:01:00]; The advent of analytics to poker, and why Annie would get crushed against today’s professionals [1:10:30]; The decision matrix, and the ‘resulting’ heuristic: The simplifier we use to judge the quality of decisions —The Pete Carroll Superbowl play call example [1:16:30]; The personal and societal consequences of avoiding bad outcomes [1:27:00]; Poker as a model system for life [1:37:15]; How many leaders are making (and encouraging) status-quo decisions, and how Bill Belichick’s decision making changed after winning two Super Bowls [1:41:00]; What did we learn about decision making from the Y2K nothingburger? And how about the D-Day invasion? [1:46:30]; The first step to becoming a good decision maker [1:48:45]; The difference between elite poker players and the ones who make much slower progress [1:55:30]; Framework for learning a skill, the four levels of thought, and why we hate digging into our victories to see what happened [1:58:15]; The capacity for self-deception, and when it is MOST important to apply four-level thinking [2:06:15]; Soft landings: The challenge of high-level thinking where there is subtle feedback and wider skill gaps [2:16:45]; The benefits of ‘backcasting’ (and doing pre-mortems) [2:19:30]; Parting advice from Annie for those feeling overwhelmed (and two book recommendations) [2:28:30]; and More. Learn more at .
#59 - Jason Fung, M.D.: Fasting as a potent antidote to obesity, insulin resistance, type 2 diabetes, and the many symptoms of metabolic illness
In this episode, Jason Fung, nephrologist and best-selling author, shares his experiences utilizing an individualized approach to fasting to successfully treat thousands of overweight, metabolically ill, and diabetic patients, and why being a doctor who specializes in kidney disease gives him a unique insight into early indications of metabolic disease. We also have a great discussion on insulin resistance where Jason makes the case that we should actually think of hyperinsulinemia as the underlying problem. We also discuss the difference between time-restricted feeding, intermittent fasting, and dietary restriction (e.g., low-carb) and how they can be used to attack the root cause of T2D, metabolic syndrome, and obesity. We also have a fascinating discussion about the limitations of evidence-based medicine which leads to a conversation where we compare and contrast the scientific disciplines of medicine and biology to theoretical physics. We discuss: Comparing scientific disciplines: Medicine and biology versus physics [7:25]; The limitations of evidence-based medicine [12:30]; Early signs of metabolic disease: How specializing kidney disease gives Jason a unique insight into early indications of illness [20:50] Insulin resistance, hyperinsulinemia, and the overflow paradigm [29:30]; Why the common treatments for type 2 diabetes seem to make things worse [42:30]; How hyperinsulinemia (not insulin resistance) drives metabolic syndrome [53:15]; Insulin and weight gain, and using fasting to empty the cells of glucose [59:30]; The two step process of developing type 2 diabetes and how they are both manifestations of hyperinsulinemia [1:03:15]; NAFLD and hyperinsulinemia: A vicious cycle [1:08:30]; Are the features and symptoms of diabetes actually protective? [1:12:15]; Is obesity causing insulin resistance or is it the other way around? [1:17:30]; What role does inflammation play in obesity? [1:21:45]; CVD and cancer: Diseases of too much growth? [1:27:30]; How to reduce proliferation with rapamycin, nutrition, exercise, fasting, and manipulating hormones [1:32:45]; Getting patients to fast: How Jason and Peter utilize fasting in their practice, and how their approach differs [1:40:15]; Comparing bariatric surgery to fasting as a treatment for type 2 diabetes [1:48:00]; Why people think that fasting is bad for you [1:55:15]; Time-restricted feeding and intermittent fasting: Defining terms, and how Jason applies them in his practice [1:58:30]; A fasting case study: A diabetic patient with a non-healing foot ulcer [2:04:00]; Keys to a successful fast [2:12:45]; Muscle loss during fasting, and why Jason isn’t worried [2:24:45]; Will fasting help a healthy person live longer? [2:31:30]; Does fasting cause gallstones? [2:38:45]; and More. Learn more at .