The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Dr. Marleah Dean Kruzel, Professor of Communication at the University of South Florida. They discuss her personal path from watching breast cancer move through her family to testing positive for a hereditary mutation herself, the ART framework she developed for managing uncertainty, and the complexities of communicating genetic risk within families.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Marleah
01:35 Marleah's family history of breast cancer across four generations
02:48 Marleah's childhood living through her mother's five-year cancer battle
04:26 Marleah's experience with genetic testing
07:19 How a positive test result reshaped Marleah’s PhD research focus
08:40 The central challenges of living with a positive test result 
10:50 The ART framework for managing hereditary cancer uncertainty
15:06 Applying the ART framework to Patrick’s experience with uncertainty and the importance of having a support system 
19:53 Common misconceptions in how families communicate genetic risk
23:54 The previvor identity and the chronic uncertainty it brings
25:40 How Marleah has learned to accept and embrace uncertainty
27:57 Balancing logic and emotion in hereditary cancer family planning
31:28 How Marleah grounds her research tools in patients' lived experience
33:21 How AI is eroding our capacity to sit with uncertainty
35:57 Redesigning healthcare for a lifespan of genetic risk information
38:10 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Dr. David Hallett, Chief Scientific Officer at Recursion. They discuss the biggest shifts in drug discovery over Dave's three-decade career, where AI is genuinely transforming the field today versus where the hype outruns the reality, and how Recursion's perturbational maps have uncovered and validated a novel neurodegeneration target.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Dave
01:57 The biggest shifts in drug discovery over three decades
06:39 Where AI is delivering real wins across drug discovery today
12:19 How AI-assisted trial simulation reveals which eligibility criteria to relax
14:46 The three biggest reasons drug programs fail in the clinic 
18:20 How Recursion's perturbational maps uncover new drug targets
24:58 A four-step framework for validating a novel drug target
28:44 How Recursion balances deep therapeutic focus with partnership breadth
30:52 Why AI can't shortcut clinical trials, and what proof of real impact looks like
34:57 The skills scientists need most in the AI era, and why trusting AI outputs starts with trusting the data
39:52 Closing remarks
Find out more:
Recursion (https://www.recursion.com/)

This week on The Genetics Podcast, Patrick is joined by Dr. Danny Miller, Assistant Professor of Pediatrics and of Laboratory Medicine and Pathology at the University of Washington and Attending Physician at Seattle Children's Hospital. They discuss the case for making long-read sequencing the first genetic test every patient receives, the reference dataset his lab is building from the 1000 Genomes Project to resolve structural variants, publicly available methylation signatures as biomarkers for diagnosis and treatment response, and his vision for genome-informed care from newborn screening through the NICU.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Danny
01:41 The case for long-read sequencing as first-line genetic testing
02:52 Current barriers to wider use of long-read sequencing 
04:14 Building a long-read reference dataset from 1000 Genomes for variant filtering
06:47 How long-read sequencing can solve a missed diagnosis 
08:12 The clinical case for complete telomere-to-telomere genomes
10:39 What it will take to shift the clinical genetics status quo
12:06 Making methylation signatures public to diagnose disease and track therapy
15:58 Danny's path from programming and finance into clinical genetics
18:19 Danny's lived experience with deafness and achondroplasia, and how it shapes his approach to genetic counseling
21:46 Danny's optimism about AI in genomics and worry about AI in education
27:15 The path to making genomes a routine part of the medical record
29:47 The vision of same-day newborn genomic data guiding NICU treatment decisions
34:31 Closing remarks
Find out more:
Miller Lab (https://millerlaboratory.com/)

This week on The Genetics Podcast, Patrick is joined by Dr. Brent Richards, CEO and Founder of 5 Prime Sciences and Professor of Human Genetics, Epidemiology, and Medicine at McGill University. They discuss how to triangulate different types of genetic evidence to validate a drug target, why herd psychology often drives which targets get funded, why strong genetic support didn't save the Zeus IL-6 trial, and how collider bias can distort genetically stratified clinical trials.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Brent
01:43 How company size shapes access to genetic drug discovery tools
04:10 Brent's framework for triangulating different types of genetic evidence
06:50 The herd psychology behind which drug targets get funded
10:01 Potential reasons the Zeus IL-6 trial failed despite strong genetic evidence
12:49 What a gold standard genetic evidence package actually looks like 
17:13 Closing the data gap with diverse genomes and systematic pipelines
19:03 The diabetes patient story that drove Brent into drug development and balancing academia with industry
25:39 Why obesity went from a drug development graveyard to its biggest frontier
29:13 How collider bias can distort genetic risk trial results
38:20 Where to go deeper on advanced genetic drug discovery concepts
40:11 Closing remarks
Find out more:
5PrimeSciences’ symposium on human genetics at ASHG2026 in October

This week on The Genetics Podcast, Patrick is joined by Dr. Andrew Jackson, Programme Leader at the MRC Human Genetics Unit at the University of Edinburgh. They discuss how his lab discovered that gain-of-function DNMT3A mutations cause both microcephalic dwarfism and an accelerated aging syndrome, and what that reveals about the shared biology of growth and aging.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Andrew
01:34 The origins of Andrew's work linking brain size and aging
02:54 The genetics of mammalian size range and epigenetic factors regulating growth
05:02 How DNMT3A mutations causing dwarfism led to discovering an accelerated aging syndrome
09:46 Cell number rather than cell size as the shared driver of growth and aging
13:07 Whether brain size within humans actually predicts cognitive ability
15:20 Why intellectual disability has far more known genes than dwarfism
19:26 Discovering ribonuclease H2's role in DNA repair, and its unexpected link to cancer 
23:35 Why studying rare monogenic diseases reveals broader biology
26:59 Andrew's next research questions on aging, cancer, and mutation biology
28:42 Why humans, model organisms, and cell assays each have a role
31:00 Somatic mosaicism's growing role in aging and disease beyond cancer
36:11 Closing remarks
Find out more:
Mentioned studies from Andrew’s lab: 
https://www.nature.com/articles/s41588-026-02633-8

https://www.nature.com/articles/s41588-018-0274-x