Behind the Breakthroughs

Inside Precision Medicine
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Aug 6, 2025 • 41min

Gonna Be (500 Miles): Unleashing CRISPR’s Clinical and Diagnostic Potential

As CRISPR, the most groundbreaking biotech discovery of the 21st century, gained traction, Janice Chen, PhD, enrolled as a graduate student in the lab of Nobel laureate Jennifer Doudna, PhD, at UC Berkeley. In contrast to the many scientists around the world who sought to use CRISPR in animal models to make the long-awaited genome edits, Chen opted to transform CRISPR from a discovery in the lab into a tool that could save lives and improve health. To achieve this, Chen, Doudna, Trevor Martin, and Lucas Harrington were co-founders of Mammoth Biosciences, a pioneering CRISPR company.Mammoth has persevered through the COVID-19 pandemic and the economic shifts in the biotech sector, mostly because of Chen's determination to broaden the scope of CRISPR and apply it to human diagnostics and health. This episode of Behind the Breakthroughs delves into that vision, revealing how Chen has played a critical role in the transformation of CRISPR from a mere concept in basic science to a miraculous medical breakthrough in the span of a decade.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Hosted by Jonathan D. GrinsteinAudio mixed and mastered by David MoselyProduced by Bill Levine Hosted on Acast. See acast.com/privacy for more information.
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Jul 23, 2025 • 41min

Uncut GEMS: Epigenetic Editing Aims to Refine Personalized Genetic Medicine

There was tragic biopharma news in mid-June 2025, when this episode was recorded. A second person treated with Elevidys, Sarepta Therapeutics' gene therapy for Duchenne Muscular Dystrophy (DMD), died from the drug. Just last week, Sarepta announced that a third clinical trial participant with limb-girdle muscular dystrophy died from liver failure caused by the experimental gene therapy, which is also suspected of Elevydis. Genetic medicines are still risky and in development, but difficulties like safety can spur innovation. This is where our special guest for this episode steps in.After 25 years of leading drug programs in "big pharma," Amber Salzman left GSK after multiple family members were diagnosed with a hereditary neurodegenerative illness. She is currently the CEO of Epicrispr, a biotech company focused on epigenomic modulation, a promising area of genetic medicine. In this episode, Salzman discusses how Epicrispr is using their Gene Expression Modulation System (GEMS) to develop therapeutics for previously untreated genetic disorders, such as those that require finer tuning than simply turning genes on and off, as well as those that are too large for gene replacement, like DMD.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Hosted by Jonathan D. GrinsteinProduced by Bill LevineAudio mixed and mastered by David MoselyMusic provided by penguinmusic Hosted on Acast. See acast.com/privacy for more information.
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Jul 9, 2025 • 40min

More than a Feeling: Predicting Biology with Spatiotemporal Multiomics

In this enlightening conversation, Mike Previte, CTO and co-founder of Element Biosciences, sheds light on his journey from Boston to groundbreaking advancements in biomedical technology. He discusses the limitations of current sequencing tools in capturing the dynamics of living cells and advocates for a 5D multiomics approach. Previte emphasizes the importance of integrating spatial and temporal dimensions in precision medicine. He also critiques traditional drug testing methods and highlights the potential of human-based models like organoids for safer and more effective therapies.
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Jun 25, 2025 • 35min

Just the Two of Us: Creating Microbiomes to Fight Cancer, ALS, and More

What do the steel industry and cutting-edge cancer treatments have in common? According to Hervé Affagard, CEO and co-founder of MaaT Pharma, more than you might think. In this episode, Hervé guides us through his journey from his early days as an engineer pioneering in industrial fields to spearheading the development of microbiome-based therapies for some of the world's most challenging diseases.Guided by a deeply personal mission inspired by his parents’ battles with cancer, Hervé shares how a revelation about the microbiome over a decade ago changed everything. From the first transformative trials on Clostridium difficile to MaaT Pharma’s work restoring microbial balance to treat graft-versus-host disease, Hervé explains how re-establishing the gut’s ecosystem can enhance immune function and offer new therapeutic possibilities for oncology and beyond.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Hosted by Jonathan D. GrinsteinProduced by Bill LevineAudio mixed and mastered by David MoselyMusic provided by penguinmusic Hosted on Acast. See acast.com/privacy for more information.
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Jun 11, 2025 • 38min

Nonsense! Engineered tRNAs Offer Universal Solutions to Stop Codon Diseases

In May of 2020, drug developer Michelle Werner, PhD, learned that one of her three children—her middle child, Caffrey—was diagnosed with Duchenne muscular dystrophy (DMD). Werner went searching for an existing or experimental cure but came out empty-handed. So, after a couple of decades as a big pharma stalwart, Werner made a major career change and took over as CEO of Flagship Pioneering company Alltrna, which had a solution she believed could help children and families in similar positions—even if not Caffrey himself.In this Behind the Breakthroughs episode, Werner talks about the experience of being a mother to a child with a rare disease and her mission as Alltrna's CEO to find cures for all rare diseases, the majority of which have no approved therapies. Michelle goes in-depth into the mechanism behind Alltrna’s engineered transfer RNAs (tRNAs) and their broad applicability to all diseases caused by nonsense mutations leading to premature stop codons.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Produced by Bill LevineHosted by Jonathan D. GrinsteinAudio mixed and mastered by Jason MackMusic provided by Artem Hramushkin Hosted on Acast. See acast.com/privacy for more information.
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May 28, 2025 • 38min

PSA on PRS: Population Genomic Screens Need More Than Pathogenic Variants

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 and build towards overcoming some of the barriers to maximizing population genomic screening for preventive medicine.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Produced by Bill LevineHosted by Jonathan D. GrinsteinAudio mixed and mastered by Jason MackMusic provided by Artem Hramushkin Hosted on Acast. See acast.com/privacy for more information.
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May 14, 2025 • 30min

You Say Goodbye (Guess-and-Check), I Say Hello (Virtual Cell)

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.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Produced by Bill LevineHosted by Jonathan D. GrinsteinAudio mixed and mastered by Jason MackMusic provided by Artem Hramushkin Hosted on Acast. See acast.com/privacy for more information.
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Apr 30, 2025 • 36min

Operation Oroborous: How Lab-in-the-loop Turns Patient Data Into Patient Care

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.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Produced by Bill LevineHosted by Jonathan D. GrinsteinAudio mixed and mastered by Jason MackMusic provided by Artem Hramushkin Hosted on Acast. See acast.com/privacy for more information.
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Apr 16, 2025 • 45min

Is Personalized Genomics Undergoing a Direct-to-Consumer Renaissance?

Kian Sadeghi, the visionary founder of Nucleus Genomics, is shaking up personalized genomics with his direct-to-consumer whole genome sequencing service. He discusses the importance of patient agency and critiques traditional insurance biases against genetic testing. The conversation dives into the ambitious future of accessible genetic testing, inspired by personal tragedy. Sadeghi also reflects on the downfall of 23andMe and shares insights on how to avoid similar pitfalls while democratizing genomics for everyone.
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Apr 2, 2025 • 51min

From Medellín to the Caribbean: Latin American Diversity’s Genetic Potential

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 this Behind the Breakthroughs episode, Bustamante explains why mapping this diversity can uncover genetic insights that will lead to better treatments for diseases that disproportionately affect these communities.Stay up to date with the latest episodes of Behind the Breakthroughs by subscribing to the IPM eNewsletter here.Produced by Bill LevineHosted by Jonathan D. GrinsteinMusic provided by Artem HramushkinAudio mixed and mastered by Jason Mack Hosted on Acast. See acast.com/privacy for more information.

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