The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Derek Ansel, Global Vice President and Therapeutic Strategy Lead for Rare Disease and Oncology at Worldwide Clinical Trials. They discuss how contract research organizations design and run rare disease trials, the challenges of selecting endpoints and patient populations, and how emerging approaches like n-of-1 therapies, regulatory flexibility, and AI are reshaping clinical development.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Derek
01:38 The role of Contract Research Organizations (CROs) in clinical development
02:41 Why endpoints are the hardest problem in rare disease trial design
05:24 How Derek’s team chooses and operationalizes endpoints in rare disease trials
08:14 Balancing patient selection, signal detection, and trial feasibility in rare disease
11:55 How the FDA’s new guidance for personalized therapies could accelerate rare disease drug development
14:20 Patient engagement, genetic counseling, and decision-making in genetic trials
19:30 Patient and clinician dynamics in genetic subtypes of common disease
23:05 What needs to change to make n-of-1 therapies scalable and accessible
26:12 Where AI is delivering real impact in clinical trials today and where it is heading
31:24 Operational bottlenecks, risk tolerance, and the limits of AI adoption in clinical trials
34:55 Derek’s path from early clinical research roles to genetic counseling and rare disease drug development
38:51 Key areas driving progress in rare disease over the next five years
41:42 Closing remarks
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This week on The Genetics Podcast, Patrick is joined by Dr. Tim Jobson, consultant physician and gastroenterologist at Somerset NHS Foundation Trust and Medical Director of Predictive Health Intelligence (PHI). They discuss the rising burden of metabolic liver disease and how routine clinical data can be used to detect disease earlier and prevent late-stage presentation. They also discuss the LiveWell study, a collaboration between Sano Genetics and PHI, and what it reveals about layering genetics and other data types to improve risk stratification and clinical trial recruitment. 
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Tim
01:50 The rise of metabolic liver disease and worsening mortality trends
04:35 Motivation and goals behind the Somerset Liver Improvement Program to address late diagnosis
09:13 Where genetics is already used in liver disease and where it’s still emerging
13:17 Current tools for staging liver disease and the challenge of predicting progression at scale
18:48 How the LiveWell study could improve risk prediction and reshape trial recruitment in liver disease
23:58 Applying longitudinal risk detection beyond liver disease to cardiometabolic and other chronic conditions
26:35 Using subtle changes in routine blood tests to identify cancer risk earlier
28:09 Using existing health data to drive earlier intervention and maximize patient impact
30:05 Expanding beyond liver disease, scaling early detection, and advancing precision medicine
32:18 Closing remarks
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This week on The Genetics Podcast, Patrick is joined by Dr. Glenn Cohen, Professor at Harvard Law School. They discuss the evolving legal and ethical landscape of reproductive genetics, why regulation in areas like embryo selection remains limited, and questions arising around the use of AI in healthcare.
Show Notes: 
0:00 Intro to The Genetics Podcast
00:59 Welcome to Glenn
01:35 An overview of the courses Glenn teaches at Harvard Law School
02:29 Glenn’s areas of expertise across biomedical ethics
03:20 Ethical considerations around reproductive medicine and polygenic risk scores
10:37 Regulatory uncertainty and limited oversight in reproductive genetics
13:18 Liability, regulation, and real-world implementation challenges for AI in healthcare
14:52 Risk–benefit framework for evaluating AI use in clinical settings
17:19 Glenn’s experience contributing to landmark Supreme Court cases in biotechnology and health law
20:09 Glenn’s perspective on mitochondrial replacement and its regulatory divide between the UK and US
22:20 Closing remarks
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This week on The Genetics Podcast, Patrick is joined by Dr. Andrea Ganna, Associate Professor at the Institute for Molecular Medicine Finland (FIMM). They discuss the promise and limits of polygenic risk scores for disease prediction and clinical trials, how large-scale electronic health records and AI models could transform medical research and healthcare planning, what Finland’s national health data infrastructure enables for population-scale studies, and how genetics can be used to strengthen trial emulation in observational data.
Show Notes: 
0:00 Intro to The Genetics Podcast
00:59 Welcome to Andrea
01:51 Andrea’s research focuses, including polygenic scores in biobanks and AI applications 
03:02 Complementarity between polygenic scores and electronic health record–derived risk signals across biobanks
04:47 Using polygenic risk scores for prognostic versus predictive enrichment in clinical trials
10:28 Limitations and opportunities of using AI models on large-scale electronic health records
15:47 Legal, data infrastructure, and privacy barriers to building AI models on health records
18:04 Choosing model architectures for healthcare AI 
19:47 Using AI and multi-omics data to integrate biological knowledge and the challenge of learning causality
21:43 How removing genetic effects from proteins improves disease prediction and highlights the role of environment
24:42 Finland’s health data ecosystem and national biobanks
28:11 Using genetics to improve trial emulation in biobank data and observational studies
33:42 Closing remarks
Find out more:
Trial emulation study

Polygenic scores study

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This week on The Genetics Podcast, Patrick is joined by Dr. Anna Lindstrand, Professor and Consultant in Clinical Genetics and Genomics at the Karolinska Institute. They discuss how Sweden has scaled whole genome sequencing as a first-line test for rare disease, what long-read sequencing adds to clinical diagnostics, how national genomic infrastructure can accelerate translation into precision medicine, and where prevention and adult genomic screening may fit into the future of healthcare.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Anna
01:34 Choosing between whole genome, exome, panels, and long-read sequencing in clinical practice
04:05 Evaluating long-read sequencing in the clinic 
06:37 What long-read sequencing adds to diagnostic yield
09:15 The role of RNA sequencing, proteomics, and methylation profiling as complementary tools in clinical genomics
13:07 Building a coordinated national infrastructure for clinical genomics and rare disease research in Sweden
18:20 The shift toward precision therapeutics and new standards for clinical actionability
23:18 Using national genomic data and registries to make Sweden trial-ready for precision therapies
27:01 Moving beyond monogenic models to capture polygenic and borderline signals in clinical genomics
30:44 Genomics for prevention including adult screening and pharmacogenomics
36:23 Anna’s research priorities for the next phase of genomic medicine and structural variant discovery
38:32 Closing remarks
Find out more:
Long-read sequencing study

Moving beyond monogenic disease paper

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