Behind the Breakthroughs

Mayo Clinic Laboratories’ new whole-transcriptome RNA sequencing assay expands the detection of clinically significant gene fusions across solid tumors, helping refine cancer diagnoses and inform targeted treatment decisions. Hussam Al Kateb, PhD, co-director of Mayo Clinic’s Clinical Genomics Lab, takes us behind the scenes of a major reference laboratory to explore the challenges of developing advanced genomic diagnostics, keeping pace with scientific discovery, and translating technological breakthroughs into precision oncology.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

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What began as a search for plant-friendly CRISPR tools led Matt Begemann, PhD, and colleagues to Cas12a2, or CasCLEAR, an unusual system that can trigger broad nucleic acid damage after recognizing an RNA target, creating potential applications in cancer therapy, diagnostics, and antimicrobials. With early studies showing promise against cancer-causing mutations, Begemann’s story highlights both the challenges of translating Cas12a2 into therapies and the value of pursuing unexpected scientific discoveries.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

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Human Longevity executive chairman Wei-Wu He discusses how the integration of genomics, advanced imaging, and artificial intelligence could transform disease prediction and personalized preventive medicine. Reflecting on Craig Venter’s legacy, he explores the challenges of democratizing precision medicine and the quest to extend human healthspan by identifying and intervening in disease before symptoms emerge.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Inside Precision Medicine (SAGE Publishing)

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Roche’s AXELIOS sequencer, Alzheimer’s blood test, and push to automate mass spectrometry point to a broader strategy of making advanced diagnostics routine. Whether AXELIOS can meaningfully challenge Illumina’s sequencing dominance, however, remains an open question.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Inside Precision Medicine (SAGE Publishing)

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Gene therapy’s biggest bottleneck remains delivery: getting increasingly sophisticated genetic medicines safely into the right cells. SonoThera is taking a radically different approach, using ultrasound and microbubbles instead of viral vectors and nanoparticles, which could allow for larger payloads, repeat dosing, and precise tissue targeting. The key question is whether this seemingly too-good-to-be-true approach can work in humans after promising results across multiple organs in animals.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Inside Precision Medicine (SAGE Publishing)

Biocatalysis has evolved from a scientific curiosity into a powerful manufacturing platform, culminating in enlicitide, the first oral macrocyclic peptide PCSK9 inhibitor. Merck’s David Thaisrivongs explains how enzyme engineering helped create this “Goldilocks” class of medicines—and could open previously inaccessible drug targets to oral therapies.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Inside Precision Medicine (SAGE Publishing)

Hosted on Acast. See acast.com/privacy for more information.

Antimicrobial resistance (AMR) isn't going to be solved by new antibiotics alone—it also requires identifying resistant infections quickly enough to guide treatment and prevent transmission. In this episode of Behind the Breakthroughs, Anne Beaubrun, PhD, of Cepheid and Amish Acharya, PhD, of the Fleming Initiative, discuss how rapid molecular diagnostics, including the TRACE-CPE study, could bring precision medicine to infectious disease by enabling earlier detection of carbapenemase-producing Enterobacterales (CPE)—dangerous, last-resort antibiotic-resistant bacteria that are spreading rapidly in hospitals. They also explore the scientific, clinical, and policy challenges of making rapid diagnostics a routine part of healthcare worldwide.

For decades, psychiatry has relied on symptom-based diagnosis and trial-and-error treatment, but precision medicine is set to transform mental health care by using objective biological measures—such as EEG, sleep and circadian rhythm data, and cognitive testing—with AI-driven analysis to match patients with the therapies most likely to work for them. In this episode of Behind the Breakthroughs, Alto Neuroscience founder and CEO Amit Etkin explains how biomarker-guided drug development and biologically defined patient populations could make precision psychiatry routine, improving outcomes and changing how psychiatric disorders are diagnosed and treated.

Produced and hosted by Jona...

AI is transforming biomedical research, but meaningful advances in drug discovery require more than just increasingly powerful algorithms—they depend on combining machine learning with physics-based simulations, mechanistic models, and rigorous experimental validation. In this episode of Behind the Breakthroughs, Michael Antonov, co-founder of Oculus and computational drug discovery company Deep Origin, shares a pragmatic perspective on AI's opportunities and limitations in medicine, explaining where it is accelerating innovation and why human expertise and experimental science remain indispensable.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

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Philippe Pouletty, MD, is one of Europe’s most successful life sciences entrepreneurs, having spent more than 30 years building category-leading biotechnology and medical technology companies from breakthrough scientific innovations. His most notable achievement is Abivax, which he founded and chaired for a decade, transforming it into a global biotechnology leader that reached an approximately $10 billion market capitalization following positive Phase 3 results in 2025. Today, he is applying the same proven strategy to Carvolix, combining breakthrough implants, AI-powered software, and autonomous mini-robotics to create a next-generation cardiovascular MedTech company focused on improving outcomes for patients with heart valve disease and stroke.

While growing up during the polio era, Arthur Caplan, PhD, saw doctors hide painful truths from families and children, which sparked his lifelong questions about power, protection, and inequality in medicine. In this episode, Caplan claims that bioethics has changed from marginalizing or abandoning disabled people to genetic testing, parental perfectionism, and personal autonomy over collective responsibility. Caplan predicts that extreme individualism will endanger public health and that the next ethical frontier will be the brain and how far humans should alter identity.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and...

Brain-computer interfaces have gained widespread attention largely for assistive applications, but Carolina Aguilar sees their greatest potential in directly treating neurological disease. Through INBRAIN Neuroelectronics, she is developing graphene-based implants designed to read and stimulate neural activity with far greater precision than conventional devices, building on insights from her 13 years at Medtronic and earlier neuroscience research. In this conversation, Aguilar explains why INBRAIN prioritizes therapeutic BCIs, how graphene could advance personalized neurotechnology and AI-driven therapies, and why conditions such as Parkinson’s disease, epilepsy, and cardiometabolic disorders are central to the company’s long-term vision.

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Matthew Rabinowitz, PhD, moved from engineering to medicine after his Human Genome Project work, motivated by both scientific insight and personal loss that exposed the limits of existing genetic diagnostics. He founded Natera and later Myome, building genomic and AI-driven tools to improve disease detection, risk assessment, and prevention. In the episode, he highlights challenges. such as regulatory barriers, fragmented data, and translating genetics into clinical decisions, while aiming to develop predictive blood tests that enable proactive care.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Precision medicine promises individualized care through data, but progress remains fragmented. Clinical, genomic, and imaging data are siloed, limiting real-world use. Jurgi Camblong, PhD, founded SOPHiA Genetics to integrate multimodal data into actionable insights, yet variability in technologies and evolving biology complicate standardization. In this episode of Behind the Breakthroughs, Camblong discusses how effective solutions require combining diverse AI methods grounded in context and longitudinal feedback loops. To Camblong, the challenge is not data quantity but making existing information usable in patient care.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and...

As an Origination Partner at Flagship Pioneering, Molly Gibson, PhD, co-founded her first company, Generate:Biomedicines, in 2018, where she made her mark by developing models that design novel proteins—work that has already led to a Phase 3 asthma drug. Since then, she has gone on to co-found two additional companies: Expedition Medicines and Lila Biosciences. In this episode, Molly explains why the anticipated boom in AI-guided drug development hasn’t fully materialized and how she’s tackling the challenge by modeling complex chemistry to synthesize novel small molecules at Expedition Medicines. She also discusses building "superintelligence" and closed-loop systems in whi...

Xenotransplantation has long been a scientifically promising but ethically complex field, overshadowed by its limited practicality despite the growing shortage of transplantable organs and the urgent needs of patients. Recent breakthroughs, including genetically modified pig heart transplants in 2022 and 2023, have demonstrated its feasibility, marking a turning point even though long-term survival has not yet been achieved. In this episode of Behind the Breakthroughs, Mike Curtis, PhD, President and CEO of eGenesis, explains how the company is building on this success to advance xenotransplantation as a scalable clinical strategy, emphasizing that even temporary extensions of life—such as a recent ni...

Traditional drugs usually inhibit specific protein sites, but many disease-causing proteins lack accessible or unique motifs, leaving them “undruggable.” Targeted Small-molecule drugs have long been the quiet workhorses of modern medicine, slipping inside cells to target disease-driving proteins, even as biologics, immunotherapies, and genetic medicines have taken center stage in recent years. Yet thousands of disease-related proteins remain “undruggable” because they lack the structural pockets needed for traditional inhibitors to bind. In this episode, Markus Warmuth, MD, CEO of Monte Rosa Therapeutics, explains how molecular glue degraders harness the cell’s protein-disposal machinery to eliminate harmful proteins e...

Cancer Research Institute CEO Alicia Zhou, PhD, traces her path from teenage lab technician to leader in cancer immunotherapy. Trained at MIT and Dana-Farber, she worked on The Cancer Genome Atlas before moving to industry at Color Genomics, expanding access to clinical sequencing. Zhou champions applying advanced genomics to immunotherapy through CRI’s Discovery Engine, an open dataset mapping tumor–immune interactions. She argues nonprofits uniquely fund shared infrastructure and standardization efforts. By supporting collaboration, young scientists, and patient resources, Zhou aims to accelerate breakthroughs and ultimately make cancer solvable.

Produced and hosted by Jonathan D. Grin...

CRISPR has crossed a turning point, evolving from an experimental tool into a platform delivering FDA-approved therapies and on-demand patient treatments that correct disease at its source. Brad Ringeisen, a former DARPA office director and leader at the Innovative Genomics Institute (IGI), has been at the center of that transition, helping guide CRISPR from early promise toward scalable clinical impact. Ringeisen discusses in this episode how he is collaborating with CRISPR pioneer and Nobel Prize winner Jennifer Doudna, PhD, at the IGI to address rare, complex, and underserved diseases, going beyond isolated successes. Accessibility, durability, and worldwide benefit, Ringeisen...

Cancer immunotherapy evolved through decades of research, with watershed moments like checkpoint inhibitor approvals and the first CAR T trial results reshaping expectations. For Zachary Roberts, MD, PhD, witnessing CAR T-induced remissions as a Mass General resident convinced him of the field’s future and drew him from academia into drug development. Now as CMO and EVP of R&D at Allogene Therapeutics, he’s focused on the next inflection point: transforming CAR T into scalable, off-the-shelf therapies that could broaden access and extend impact beyond cancer to autoimmune disease.

Produced and hosted by Jonathan D. Grin...

Geroscience sits between hype and skepticism, with headlines swinging from dubious mouse-life supplements to ethically distant fantasies like organ or head transplants. Yet precision medicine has been turning science fiction into reality. Today’s guest, Boyang Wang, thinks lifespan extension is next. Founder of Singapore-based Immortal Dragons, he backs longevity companies—from organ printing to preventive gene therapies. A former computer scientist and tech entrepreneur, Wang now runs a $40M fund supporting underfunded bets on healthspan and aging.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Br...

In this episode, I’m joined by Kevin Davies, PhD, Director of Professional Media Content Development at Sage Publications and acclaimed author of Editing Humanity, one of Jennifer Doudna’s favorite books on CRISPR. We explore key themes in precision medicine in 2025, including personal genomics, gene editing, and clinical impact. The discussion centers on my personal genomic testing series, major gene-editing advances, and emerging debates around embryo selection and IVF-based genomics heading into 2026.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Insi...

Precision medicine isn’t just molecular—it’s anatomical. Even as gene editing advances, many conditions still demand exquisitely targeted surgical care. That’s the world envisioned by Stereotaxis CEO David Fischel, where operations become remote, cockpit-guided missions. Using magnetic “invisible fingers,” surgeons steer ultra-soft catheters with sub-millimeter precision through fragile vessels. After two decades and 170,000 patients, Stereotaxis has reshaped cardiac procedures into robotic navigation—bridging genomics, anatomy, and the future of intervention.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brought to you by Inside Precisi...

Katherine Stueland’s early advocacy—raising money for genetic disease research as a child—shaped her belief that genomic insight can change lives. As CEO of GeneDx, she has refocused the company on high-need conditions, tripled sequencing capacity, delivered more than 750,000 exomes and genomes, and returned the company to profitability. She highlights the power of combining sequencing with the Infinity database and champions newborn screening, all guided by a core principle: genomic access should reach every family.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by Erick Ziegler

Brough...

When Rahul Gupta, MD, MPH, stepped down in January 2025 as Director of the White House Office of National Drug Control Policy, he closed a historic chapter as the first physician and first immigrant to serve as America’s “drug czar.” He steered national drug policy toward a public-health approach, advancing harm reduction, expanding naloxone access, and reframing addiction as a treatable condition amid the deadliest years of the fentanyl crisis. Now, as President of GATC Health, Gupta is channeling his experience into biotechnology and AI, seeking to accelerate drug discovery and use data-driven tools to outpace the slow machinery of gov...

If you work in biotech, the name Langer likely rings a bell. Robert Langer—the MIT legend behind Moderna and dozens of biotech startups—has become synonymous with innovation. Now, a new Langer is stepping forward. Michael Langer, Robert’s son, represents a new generation of investors rethinking biotech in the age of AI and data. Rather than chasing hype, he’s applying lessons from a lifetime around scientists to build a more disciplined, informed investment philosophy. As co-founder of T.Rx Capital, he’s helping shape the next phase of tech-enabled biotech—and exploring what truly drives success in precision...

When a rare genetic mutation left baby KJ without any treatment options, scientists and regulators confronted a profound ethical question: should medicine move fast enough to save a single child? For geneticist Vanessa Almendro-Navarro, PhD, KJ’s case represented both an urgent humanitarian mission and a glimpse into the future of personalized medicine. In this interview, she explains how her team created a bespoke gene-editing therapy for KJ, what it reveals about the rise of one-patient medicines, and how unprecedented collaboration is reshaping the boundaries of science and ethics.

Produced and hosted by Jonathan D. Grinstein, Ph...

Shana Kelley, PhD, embraces bold, science-fiction-like challenges, such as developing real-time technologies to monitor immune activity—work that demands cross-disciplinary expertise, flexible funding, and visionary leadership. As a Professor at Northwestern University and President of the Chan Zuckerberg Biohub Chicago, she advances “instrumented tissues” to precisely measure biological processes, sharing her passion and insights on innovation in this episode of Behind the Breakthroughs.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine (SAGE Publishing)

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Mara Aspinall has long been a leader in precision medicine, championing diagnostics as vital to better treatments and saving lives. She built Genzyme Genetics into the nation’s top testing business, later acquired by LabCorp for $1 billion, and led Ventana (now Roche Tissue Diagnostics) in pioneering companion diagnostics. As co-founder of BlueStone Venture Partners and partner at Illumina Ventures, she continues shaping the field. She also publishes the Diagnostics Year in Review, serves on multiple boards, and co-founded ASU’s School of Biomedical Diagnostics. This episode explores both her vision for testing and her journey to becoming a transformative lead...

David R. Liu, PhD, Harvard and Broad Institute professor, invented base and prime editing—gene editing tools now in 20+ clinical trials with early wins against sickle cell, leukemia, and more. Founder of Editas, Beam, and Prime Medicine, and winner of the 2025 Breakthrough Prize, Liu joins Behind The Breakthroughs to share how chemistry and evolution are driving the next wave of medicine.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine (SAGE Publishing)

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Janice Chen, PhD, helped transform CRISPR from a lab discovery into a life-saving tool. As co-founder of Mammoth Biosciences with Jennifer Doudna, Trevor Martin, and Lucas Harrington, she’s driven efforts to harness CRISPR for human health and diagnostics. On Behind the Breakthroughs, Chen shares how she’s turning a once-theoretical gene editor into a medical revolution.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine (SAGE Publishing)

Hosted on Acast. See acast.com/privacy for...

With recent safety setbacks in gene therapy underscoring the risks of genetic medicine, Amber Salzman, PhD, is charting a different course. After 25 years in big pharma, she now leads Epicrispr, where their Gene Expression Modulation System (GEMS) fine-tunes gene activity to tackle diseases too complex for traditional gene replacement, including Duchenne muscular dystrophy. On Behind the Breakthroughs, Salzman shares how epigenomic modulation could open new frontiers in treatment.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine...

Think Good Will Hunting—but in biology. Mike Previte, PhD, once at Illumina and now CTO and co-founder of Element Biosciences, is building tools to move beyond DNA and RNA sequencing toward a true 5D view of life. On Behind the Breakthroughs, he explains how technologies like AVITI 24 could unlock predictive precision medicine by revealing how cells behave across time and space.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine (SAGE Publishing)

Hosted on Ac...

Hervé Affagard, CEO and co-founder of MaaT Pharma, traded industrial engineering for medicine after cancer struck his family. Now, he’s pioneering microbiome-based therapies to restore balance in the gut, boost immunity, and tackle diseases from graft-versus-host to cancer itself. On Behind the Breakthroughs, Hervé shares how reimagining our inner ecosystem could transform treatment.

Want me to make this one lean even harder into the industrial-to-biotech transformation angle for extra contrast?

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

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When Michelle Werner, PhD, learned her son Caffrey had Duchenne muscular dystrophy, she left big pharma to lead Alltrna—a Flagship Pioneering company engineering tRNAs to tackle rare diseases with no treatments. On Behind the Breakthroughs, Werner shares her journey as both mother and CEO, and how Alltrna’s approach could unlock therapies for thousands of conditions caused by nonsense mutations.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered by David Mosely

Brought to you by Inside Precision Medicine (SAGE Publishing)

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Public health is greatly benefiting from population genomics screening, as it provides patients with risk education and treatment for symptoms of life-threatening diseases that they would not have been aware of through routine checkups. So, why hasn't population genomic screening realized its full potential? As an internist geneticist and Medical Affairs Director at Helix, this issue became all the more real for Cassie Hajek, MD, when she was diagnosed with breast cancer that evaded existing genetic testing procedures. In this earnest episode, Hajek shares how her experiences as both a cancer patient and a practitioner have helped her identify...

Three biotech trailblazers—Patrick Hsu (co-founder of the Arc Institute), Serge Saxonov (co-founder and CEO of 10x Genomics), and Gilad Almogy (co-founder and CEO of Ultima Genomics)—join forces to discuss their groundbreaking collaboration on the virtual cell. This ambitious project leverages advanced AI and cutting-edge genomic technologies to model and predict cellular behavior, a leap forward in understanding complex biological systems. The trio dives deep into their shared vision, explaining how their partnership is redefining scientific research and pushing the boundaries of what’s possible in drug discovery and precision medicine.

Produced and hosted by Jonath...

For years, Tempus operated in mystery—its website sparse on details while headlines announced massive funding and high-profile partnerships. The claim? AI-enabled solutions for personalized healthcare. Intrigued, I sought answers. In this episode, Kate Sasser, PhD, Chief Scientific Officer at Tempus, shared insights into how the company uses AI to analyze unstructured clinical data to develop patient-derived organoid models for therapeutic refinement. Most exciting is their vision of an interconnected “lab-in-a-loop” system—a cycle of real-world data, biological modeling, and AI analysis.

Produced and hosted by Jonathan D. Grinstein, PhD

Audio mixed and mastered...

At just 25, UPenn dropout Kian Sadeghi is betting big on personalized genomics. As founder of Nucleus Genomics, he’s offering affordable whole-genome sequencing direct to consumers and rethinking how patients, clinicians, and insurers engage with genetic data. On Behind the Breakthroughs, Sadeghi unpacks the fall of 23andMe, the rise of patient agency, and why he thinks genomics needs its own Bill Gates.

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Produced by Bill Levine

Hosted by Jonathan D. Grinstein

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Imagine a future where your ancestry not only tells a story about your past but also holds the key to your health. That's the vision drives Carlos D. Bustamante, PhD, population geneticist and founder of Galatea Bio, as he embarks on an ambitious mission: building a biobank of 10 million genomes to transform drug development and healthcare across Latin America. With thousands of founder populations scattered across the region—from the valleys of Medellín to the islands of the Caribbean—Latin America is a goldmine of genetic diversity. Yet, until now, it has been largely overlooked in genomic research. In th...