Mendelspod Podcast

Most of the news coming from Illumina has had to do with their leadership in the sequencing instrument space. What is lesser known is that they offer an end-to-end solution for the clinical lab, including variant calling and genome interpretation.In this podcast, we’re joined by Sam Strom, Principal Scientist at Illumina and a certified Clinical Lab Director.  Sam comes to Illumina from the clinical testing side; for example, he’s co-chair for the expert curation panel for Parkinson’s Disease and sits on a working group at ClinGen.In the interview, Sam addresses two of the big challenges in clinical sequencing, which are variant calling and variant interpretation. Sam says Illumina has created its own multi-sample genomic reference and is also making use of artificial intelligence to improve variant calling. He also shares how Illumina supports scaling variant interpretation for genomes and other assays with an AI and automation comprehensive solution, enabling high-quality genetic testing workflows to reach next level accessibility.“I think we’re going to see more “lights out” testing where there really isn’t an interpretation component to the test.   It’s a pure technical test.  It has certain limitations.  But it gets you 99.9% of the way there.  The technology is ready." 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

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comToday, we feature a new DNA synthesis company out of Sweden that is making a name with long, single-stranded DNA at scale. How long? Over 10,000 bases. Why single-stranded vs. genes? And what is meant by scale?According to Cosimo Ducani, CEO and co-founder of Moligo Technologies, the business of making DNA is just getting started.  So much for thinking it was a mature business in the early 2000s when Integrated DNA Technologies (IDT) dominated the market.

Jennifer Wipf of Ginkgo Bioworks discusses the revolutionary potential of RNA therapeutics and cell therapies in medicine. Ginkgo Bioworks aims to make engineering biology easier through automation and data fusion. The discussion delves into the challenges and promises of accessing the cell for therapeutics, as well as Ginkgo's recent acquisitions to enhance its AI capabilities.

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comChapters:0:00 Number one unmet medical need for dogs6:25 Using “extra label” for cross species12:57 Ideal for understanding human cancers21:25 Playing catch-up with human medicine28:04 1,000 pet clinic customersPrecision medicine for dogs?— as in tumor profiling for the right therapies to treat man’s best friends at the right time? Yes, that’s right. …

There’s a new genome editing company that everyone is talking about this year.  Tome Biosciences came out of stealth in December, claiming the ability to insert DNA sequences of any size at any location across in vivo and ex vivo modalities. Their website says they’re “taking us into the final chapter of medicine.”Tome’s CEO, Rahul Kakkar, joins us today on the program.  He’s a physician-scientist (cardiology) who has previously led a couple of biotech companies, Pandion Therapeutics and Corvidia Therapeutics, through initial funding and acquisition.  Rahul says that even though we’ve seen incredible breakthroughs in the gene therapy arena, all of the current editing technologies are “profoundly limited.”  That includes the technology for the first CRISPR-based drug approval, Casgevy.“Gene therapy today is putting a gene into a cell that has no relationship to the genome itself.  It’s quite unrefined.  From a clinical perspective, their impact is limited because their technology is limited.”Why so limited, and what is this great advancement in editing technology that everyone is talking about?  Rahul says the tech is able to “reprogram” a cell.What are the history and current state of the company and this new technology?  How are they dealing with the infamous “off-target effects?”  And what is the overall opportunity?Rahul talks in grand terms.  He says there is a need for genomic-based therapies if we’re going to move medicine away from treating to curing disease.   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

Exploring the impact of long reads at scale in sequencing technology. Discussing the decision between long and short reads. Plans for future instruments and insights into competing technologies.

Why aren’t more folks receiving genetic testing?In a study published in JAMA last year, Stanford cancer researcher Alison Kurian found a surprising gap between those who need genetic testing and those who receive it.  Among more than a million patients with cancer, only 6.8% underwent germline testing.Today, we begin a new series exploring this gap in testing with Robert Michel.  He's the Editor-in-Chief at The Dark Report, reporting on the laboratory industry since 1996.   Robert says the problem is multi-faceted and argues that the leading cause is that it takes years for physicians to learn about a new area of medicine.“Factor number one is simply the speed of genetic science,” says Robert.  "You’ve got to train the physician and for them to be able to incorporate genetics in their practice.  It can take years for the average practitioner.  Part two,” he says, "is reimbursement.”We spend the bulk of the interview discussing the role of pathologists in genetic testing, who he refers to as "the guardians of the medical purse."Robert also puts on the leading conference in the lab testing industry, the Executive War College Conference on Diagnostics, Clinical Laboratory, and Pathology Management.  The conference for 2024 is coming up from April 30th to May 2nd in New Orleans. 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

Batten disease is a group of neurodegenerative lysosomal storage disorders that result from pathogenic variants in one of 13 CLN genes. Collectively, Batten disease affects approximately 1 in 100,000 individuals worldwide, making it the most common pediatric neurodegenerative disorder. The most common form of Batten Disease, CLN3 disease, is a rare and fatal autosomal recessive disorder caused by mutations in CLN3. Individuals with CLN3 disease typically experience vision loss in early childhood, followed by seizures, motor and cognitive decline, and premature death by the third decade of life. Importantly, despite decades of intense research, specific biomarkers of disease status have not been reported, hindering the clinical development of therapies.Today, two researchers join us to talk about how their use of new proteomics tools has pushed their biomarker research forward in novel ways. Jon Brudvig is the Director of Discovery Research and Gene Therapy at Amicus Therapeutics, where he leads biomarker discovery in neurogenerative disease.  He is also an Assistant Professor in Pediatrics at the University of South Dakota. Bruce Wilcox is the Chief Technology Officer at PrognomiQ which is focused on early cancer detection and treatment. “Proteomics technology and the enthusiasm for it are advancing rapidly.  Proteomics is at the stage where it is translating to tools that will help physicians and patients,” says Bruce.   "It’s a lot of fun to talk about what we work on, not just from a research standpoint, but for the impact that is coming from this work." 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

After ten years, the human brain mapping project has achieved some major milestones, says Tom Nowakowski, a researcher at UCSF, on today’s program.  He says that mapping the brain is a “moon shot” easily on par with the Human Genome Project.So much of biology is basic quantification.  Brain scientists are beginning to quantify how many kinds of brain cells there are.  They are learning more about the function of various cells such as glial cells..  And they are developing a common language with each other.  A few years ago, if you put two brain scientists in a room together, they would not know how to speak to each other.One of the major technologies that have enabled this new quantification and characterization of the human brain is spatial genomics. Tom and other scientists have learned that there are 5,000 transcriptomic clusters that they associate with cell type. '“If you told me ten years ago when I was finishing my Ph.D. that one day we’d be making real progress on neurological and neuropsychiatric disorders without having to rely on a mouse model.  I would think it was unthinkable.  Here we are; we finally have technologies where you don’t need transgenic mouse models to make progress.  That is just terribly exciting.” 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

Karen Tumulty, a political writer for the Washington Post, was diagnosed with multiple myeloma. She was told she had five years to live.  Then she went to book club with friends. On the way home she came out about her diagnosis—and that changed her life.  Someone in the car happened to be the President of the Personalized Medicine Coalition, Ed Abrahams.  He made a referral and that led to better treatment and better survival. Karen’s story, along with that of her brother, is a must-listen for everyone involved in healthcare.  How does Karen’s story line up with the industry’s stories we tell ourselves? Does she think that the tale of precision medicine is getting out there?“What blew me away at the recent conference,” she says, “was that so many amazing medical advances that I was thinking were way over the horizon are here.”Are they really here, if people have to be in the right book club to hear about them? 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