Mendelspod Podcast

• The Best of Times, the Worst of Times: Former NHGRI Director Eric Green on a Shaken NIH and Surging Genomic Science

  At the end of each year we look for a guest who in many ways defines the year. Today we sit down former NHGRI director Eric Green to reflect on the most turbulent year in his 31-year career at NIH. After leading the National Human Genome Research Institute for more than 15 years, Green’s appointment was abruptly non-renewed—a decision he learned about with “two or three days notice that I was going to have to retire from federal service.” What followed, he says, was a wave of terminations and forced retirements across NIH that left NHGRI “in trauma” as entire communications, education, and policy groups disappeared overnight.Yet alongside this institutional upheaval, Green describes a scientific landscape moving at astonishing speed—from the maturation of genome editing and long-read sequencing to the rise of multi-omics and the accelerating push toward routine healthy newborn genome sequencing. He believes widespread newborn sequencing is no longer a distant vision but “within striking distance,” driven by global studies, new U.S. programs, and rapidly falling costs.The conversation also explores the political pressures shaping genomics today, especially around the collection of heterogeneous genomic data and the cultivation of a diverse workforce. Green argues that scientists must learn to explain their work in human terms—as stories about patients and cures, not grants and budgets. He says it might also be a good idea to not use the “d” word (for example, “assortment” rather than “diversity”) in grants for now, silly as that is.Despite the personal and institutional losses of the past year, Green remains committed to the future of U.S. biomedical science which continues to surge in the headlines each day. In a reference to Dickens, he says it is literally the best and worst of times.Now entering what he calls “version 3.0,” Green sees his role as genomics evangelist, educator, and advocate—helping ensure that the momentum of genomic medicine continues even as the nation’s scientific infrastructure undergoes profound stress.“I am officially on call to help rebuild the NIH… It’s very easy to destroy a place, and very hard to rebuild it.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

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• From the Archives: Next-Gen MRD Testing: Foresight’s Leap in Sensitivity with Jake Chabon and Dave Kurtz

  Note: This show was originally published on September 11, 2025. In light of the recent acquisition of Foresight Diagnostics by Natera, we’re re-publishing the interview with co-founders Jake Chabon and David Kurtz.Catching a cancer relapse before any scan could see it is the ultimate goal for minimal residual disease or MRD testing. And it’s the promise behind Foresight Diagnostics, a Stanford spin-out co-founded by scientist Jake Chabon and oncologist David Kurtz who say they have arrived at “next gen” MRD testing. In this debut interview, Jake and Dave walk us through their journey from academic research to launching one of the most sensitive MRD tests on the market—one that’s already shaped new NCCN guidelines.* 0:00 Origin story* 4:45 What makes this “next gen?”* 10:15 How do you get the leap in sensitivity* 15:45 Already had an impact on NCCN guidelines* 23:00 Launching lymphoma texting next year, then on to solid tumors* 28:00 How will this change standard of care?Jake explains how their novel PhasED-Seq technology, which tracks “phased variants”—usually two or three mutations on the same DNA molecule—enables unprecedented sensitivity, detecting cancer cells at levels as low as one part in 10 million. “It’s extremely unlikely to have two concurrent sequencing errors,” says Jake. “That’s functionally the core insight here.”For Dave, who still treats lymphoma patients, the clinical need is personal. “Our goal is to treat patients until there are no more cancer cells in the body. So having a tool that tells you when there are no more cancer cells left is kind of our holy grail.”Their MRD test, called Foresight CLARITY, launches first for lymphoma next year, with solid tumor applications in development. As their data have already begun to reshape the standard of care, Jake and Dave discuss a future in which MRD testing could come before PET scans—or even replace them.“We want MRD testing to become the standard of care across all cancers treated with curative intent,” says Jake. With Foresight CLARITY already in three prospective trials and in NCCN guidelines, and a clear clinical need, that vision may not be far off. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

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• Petter Brodin of Karolinska: How Spatial Interactomics Could Transform Autoimmune Therapy

  This week on Mendelspod, we speak with Petter Brodin, Professor of Pediatric Immunology at the Karolinska Institutet and Director of Systems Immunology at Imperial College London, about his pioneering work in childhood immune development and his new spatial-proteomics investigations into lupus.Petter shares how a single lecture on natural killer cells pulled him into immunology, and how early twin studies convinced him that “our immune systems are shaped predominantly by non-heritable factors.” That insight drove him to study the earliest stages of immune development—when newborns leave a sterile environment for a microbial world that imprints their immune trajectories for life.A major theme of the conversation is Petter’s insistence that immune responses cannot be understood by looking at cells one by one. As he puts it: “Cells don’t ever work in isolation, but historically we’ve always been studying them in isolation—and I think that’s fundamentally problematic.”This systems view is now being partly enabled by Pixelgen’s spatial interactomics. Using their Proximity Network Assay, Petter’s group is finding that lupus B cells don’t just differ in protein expression—they differ in protein distribution, revealing organization patterns that classical flow cytometry cannot capture.These spatial signatures may point directly to new, more precise therapies. Petter explains: “If there is a difference in protein–protein interaction or protein distribution that characterizes disease, then surely that indicates a dysregulation—and that is something we can target.” Instead of broad immunosuppression or depleting whole cell populations, future treatments could focus on the exact cell states driving autoimmunity.Petter ends on an optimistic note: spatial interactomics won’t just help treat autoimmune disease—it may allow us to intervene earlier, even preventatively, as we learn how early-life immune disturbances set the stage for disease decades later. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

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• From GWAS to EWAS: Chirag Patel and and Gary Miller on the Rise of Exposomics

  What if the next leap in human health isn’t hidden in our genes, but in everything that happens to them? In this week’s truly groundbreaking Mendelspod episode, we open a new chapter for the show: our first deep dive into exposomics—the study of all the physical, chemical, biological, and social exposures that shape the human body across a lifetime.To guide us, we welcomed two leaders at the center of this emerging field: Chirag Patel of Harvard and Gary Miller of Columbia University, fresh off organizing Genomics Meets Exposomics, a landmark meeting held at the Mendel Museum in Brno—the birthplace of modern genetics. In the same abbey where Mendel tended pea plants, genomics and exposomics researchers from Europe and the U.S. gathered for the first time to build a shared roadmap for understanding how genes and environment interact to drive disease.In our conversation, Chirag and Gary explain why the genome alone can’t answer the biggest questions in human health. While genomics accounts for roughly 20% of complex disease risk, the remaining 80% lies in our exposures—pollutants, diet, geography, stress, microbes, medications, and more—and the fingerprints these exposures leave on our biology. Exposomics, as Gary notes, is about moving from studying one factor at a time to systematically measuring the thousands of signals that accumulate in our tissues and blood.A major theme of the discussion—and the inspiration for our episode title—is Chirag Patel’s call for exposomics to follow the same playbook that transformed genomics in the early 2000s. Just as genome-wide association studies (GWAS) revolutionized how we identify genetic contributors to disease by moving beyond one-gene-at-a-time thinking, Patel argues that the field now needs exposome-wide association studies (EWAS) to systematically search for environmental drivers. “If we are to do an exposome-wide association study… we can now discover things that were missing,” he explains, shifting from narrow, candidate-factor approaches to broad, data-driven discovery.Both guests describe a field gaining momentum thanks to better measurement technologies, large biobanks, geospatial data, and new analytic frameworks inspired by genome-wide association studies. They also speak frankly about the remaining hurdles. As Chirag puts it, one of the major challenges is not just correlating exposures with disease but determining what these findings mean for people: “There’s a number of questions that come after that…how do you modify it? Is it causal? How do we remove it from the population if it’s adverse?”Gary, who has spent decades studying Parkinson’s and Alzheimer’s, explains how high-resolution mass spectrometry now allows researchers to see exposure signals that were invisible before—sometimes even in decades-old blood samples. And looking ahead, he offers a clear note of optimism about exposomics’ readiness for scale: “We can do this now. It’s a reality.”For long-time Mendelspod listeners, the episode marks an inflection point. After fifteen years covering genomics and the multi-omic revolution, this conversation shines a light on the other half of human biology—the environment—and what may become the next major frontier in disease prevention, drug development, and precision health. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

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• Agilent Partners with PacBio to Speed Adoption of Long Reads into Diagnostic Testing

  After more than a decade of success in research, long-read sequencing is more and more adopted into clinical testing. In today’s show, we speak with Rita Shaknovich, Chief Medical Officer at Agilent Technologies, and Sarah Kingan, Associate Director of DNA Applications at Pacific Biosciences (PacBio), about how their collaboration is speeding up this long-anticipated transition.* 0:00 Long read sequencing changing clinical landscape* 7:00 Long reads replacing older technologies* 13:15 Agilent/PacBio partnership – speeding up adoption* 16:00 Panels designed for short reads can be used for long reads* 24:25 Democratizing accessLong-read sequencing—once prized mainly by researchers for its ability to resolve structural variants, repeat expansions, and complex genomic regions—has reached a point of technical and economic maturity that now makes it viable in the clinical setting. “We can now see regions of the genome that were long considered dark matter,” says Shakhnovich. “That’s leading to improved diagnostic yield and, most importantly, better outcomes for patients.”Agilent brings to this collaboration a long-standing foothold in laboratory testing. Its automated platforms and target enrichment chemistries are already embedded in many diagnostic laboratories worldwide. PacBio, of course, brings the power of HiFi long-read sequencing to the table. Together, the companies are demonstrating that technologies originally designed for short-read sequencing can be seamlessly adapted to long-read workflows. “Panels that were designed for short reads can be used for long reads—essentially right out of the box,” explains Kingan. “It really just opens up a whole world of clinical applications immediately.”By combining Agilent’s infrastructure and expertise with PacBio’s long-read innovation, the partnership is accelerating the integration of comprehensive, single-platform sequencing into patient testing. The result is a streamlined, cost-effective approach that reduces the need for multiple assays while providing richer genomic insight. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

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