Behind the Breakthroughs

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

Brought to you by Inside Precision Medicine (SAGE Publishing)

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

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)

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

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)

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

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)

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

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.

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.

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 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.

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

Brought to you by Inside Precision Medicine (SAGE Publishing)

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

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.

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.

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 mastered by Erick Ziegler

Brought to you by Inside Precision Medicine (SAGE Publishing)

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