Summary: 

This week on The Genetics Podcast, Patrick is joined by Tim Spector, Professor of Genetic Epidemiology at King’s College London and co-founder of Zoe. They discuss surprising insights on heritability from decades of twin research, the profound impact of the microbiome on health and disease, and the effect of diet on the gut microbiome. 

Show Notes: 

0:00 Intro to The Genetics Podcast

00:58 Welcome to Tim and his journey from clinical medicine to pioneering twin studies and uncovering the heritability of diseases and traits

07:20 Exploring missing heritability and why twin studies and GWAS offer different answers

10:37 What a global mega twin registry could reveal about epigenetics, environment, and disease

13:40 Findings from a twin microbiome study and how that evolved into a new chapter in Tim’s research career

16:50 The profound impact of the microbiome on health

21:08 Evolution in microbiome research techniques, microbe-diet associations, and the need for longitudinal studies 

27:00 Potential reasons why fecal transplant did not turn out to be as effective as predicted

28:53 The importance of balance in the gut microbiome and how it can be involved in cancer and the drug response

35:54 Barriers to translating microbiome science into healthcare 

38:38 The impact of microplastics and ultra-processed foods on the microbiome

41:27 Moving away from diversity measures for evaluating the microbiome and towards a more comprehensive score metric

44:36 Closing remarks with information on Tim’s upcoming book as well as Zoe products and app

Find out more

• Zoe (https://zoe.com)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: 

This week on The Genetics Podcast, Patrick is joined by Daniel Geschwind, Professor, Senior Associate Dean, and Associate Vice Chancellor of Precision Health at UCLA. They discuss the circuitous career path that led Daniel to building a biobank that provided the foundation for autism genetics, the complexity of the molecular and genetic aspects of autism, and how gene therapies could advance treatment. 

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Daniel and how he transitioned from being a chemistry teacher and consultant to an academic clinician

05:51 How a year filming ski movies helped Daniel decide what he wanted to do after college

07:29 How Daniel got started in autism research and established a biobank that built the foundation for autism genetics

11:38 Our current understanding of autism on the molecular and genetic levels

18:04 The spectrum nature of autism and how it correlates to molecular and genetic differences 

25:13 The potential convergence of variants of autism on common pathways and corresponding therapeutics

31:18 Evidence for the early developmental etiology of autism and the complexity of the genetic aspect

35:56 The developmental window for gene therapies in autism and the need for concurrent training  

38:41 Successes and barriers to data sharing and collaboration, and the importance of biobanks and functional mapping

51:40 Developing computational tools for a network approach to transcriptomes

55:28 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: 

This week on The Genetics Podcast, Patrick is joined by Helen O’Neill, molecular geneticist, founder of Hertility Health, and associate professor at University College London (UCL). They discuss how Helen’s experience as an identical twin sparked her interest in genetics, her firsthand account of the CRISPR baby controversy, and why stubborn perceptions and sensational headlines continue to cast a shadow over the gene editing field, despite major scientific progress.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Helen and an overview of her career path and how being an identical twin sparked her interest in genetics

04:57 Technology shifts in embryonic and fetal biology over the span of Helen’s career

06:44 Helen’s firsthand account and reflections on the 2018 CRISPR baby controversy

11:56 Evolution of gene editing in the face of a stubborn perception of it

15:17 Findings from Helen’s recent study on the impact of genetic screening on embryo viability and the case for genome editing in IVF patients

20:09 The stalled progress of germline genome editing in the context of regulation and public opinion 

24:08 How newborn genome sequencing could transform early diagnosis and reproductive decision-making

26:13 The origin story for Hertility Health and how it’s transforming women’s access to fertility care

32:14 The strong impact of personalized health recommendations 

33:19 Challenges in using genetics to diagnose women’s health conditions and the vision for a longitudinal biobank

35:54 Future directions in Helen’s work on women’s health and genome editing

37:21 Closing remarks 

Find out more

• Hertility Health (https://hertilityhealth.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Giles Yeo, geneticist and author of Gene Eating: The Science of Obesity and the Truth About Dieting and Why Calories Don't Count: How We Got the Science of Weight Loss Wrong. Giles and Patrick discuss the genetic, neural, and evolutionary drivers of obesity, the advancements in safe and effective obesity drugs, and the narratives around calorie counting and ultra-processed foods.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Giles and an overview of recent advances in obesity treatment

04:28 How incretin-based therapies such as GLP-1 receptor agonists have enhanced our understanding of obesity 

06:46 Unexpected effects of GLP-1-based therapies on neurodegenerative disease and addiction

09:39 Relative safety and potential side effects of GLP-1-based therapies

11:18 The gap in genetic characterization of individuals with different responses to GLP-1-based treatment

13:10 Competition and demand in the market for obesity drugs

15:46 Targeting comorbidities and genetic and neural components of obesity 

19:09 Evolutionary aspects of obesity and how modern world factors can increase risk

24:26 The role of choice in dietary habits

26:29 The spectrum of genetic influences on body weight

29:50 Next frontiers in obesity research and opportunities from genetic advances

32:52 The controversial premise of Giles’ second book on why calorie counting misses the point in improving diet and health

37:43 Giles’ nuanced perspective on ultra-processed foods

44:46 Future avenues for Giles’ research, including mapping genetics and neural circuits underlying obesity

46:05 Giles’ writing process and plans to write a third book   

48:55 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Madhuri Hegde, SVP and Chief Scientific Officer of Revvity. They discuss Revvity’s advances in ultra-rapid clinical-grade sequencing, opportunities, challenges, and global inequities in newborn screening, and the dilemma of resequencing versus long-term data storage.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Madhuri

01:52 Rebranding Revvity as a healthcare company

02:51 Advancements in sequencing and Revvity’s projects, including newborn screening tests and clinical ultra-rapid sequencing

12:29 Opportunities and challenges for newborn sequencing and global inequity in access

17:46 Price of sequencing and data storage versus resequencing considerations

21:10 Complexities and nuances of genomic data interpretation

23:28 Rethinking data portability and storage across the lifespan

26:00 Understanding penetrance and population genetics through lifelong sequencing

27:36 Scaling genetic counseling to match advancements and the potential value of chatbots

32:45 The promise of proteomics and translating Olink data to the clinic

34:31 Implementing polygenic risk scores in clinical management  

37:12 Transitioning from academia to industry and insights into product development

38:37 Closing remarks

Find out more

• Revvity (https://www.revvity.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Dr. Euan Ashley, Chair of the Department of Medicine at Stanford, founder of various biotech companies, and author of The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them. They discuss Euan’s groundbreaking work on ultra-rapid genome sequencing and how widespread sequencing, wearables, and AI could shape the future of preventive medicine and human performance.

Show Notes: 

00:00 Intro to The Genetics Podcast

01:00 Welcome to Euan

01:50 A pivotal case in Euan’s career involving diagnosing a newborn experiencing cardiac arrest

06:41 How Euan’s team worked towards a record of eight hours from clinical sample to diagnosis

10:05 Hurdles that need to be overcome before ultra-rapid sequencing workflows can be widely used in clinical settings

11:40 Considerations around widespread genetic screening in newborns

16:10 Weighing utility and uncertainty in genetic testing for disease

19:17 Steps to a future where widespread genetic testing is economically viable 

23:54 New frontiers of clinical genomics, including integration with electronic health records (EHRs) and wearables 

28:24 The physiology and genetics of athletic performance and the inspiration behind the ELITE study

33:54 Psychological drivers and effects of human performance

37:57 Euan’s interest in generative AI for developing novel therapies

41:32 Closing remarks 

Find out more

• The Ashley Lab (https://ashleylab.stanford.edu/)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Kent Rogers, Chief Executive Officer at EveryONE Medicines. They discuss Kent’s journey across every side of the desk in the drug discovery space, EveryONE Medicines’ efforts to develop antisense oligonucleotides for ultra-rare diseases, and the need to adapt regulatory models for n-of-1 therapies.

Show Notes: 

00:00 Intro to The Genetics Podcast

00:59 Welcome to Kent and his experiences across every side of the pharma ‘desk’

06:00 Challenges of commercialization for ultra-rare disease therapies and the advantage of antisense oligonucleotides (ASOs) 

10:28 EveryONE Medicines’ approach to regulatory bodies

12:30 Regulatory feedback and expectations from EveryONE Medicines’ platform-based approach to n-of-1 therapies

15:47 Differences in regulatory requirements for rare disease across countries 

19:53 Insights from being on different sides of the drug development industry

22:40 Differences in healthcare systems across countries that can facilitate or impede drug development

26:57 Rationale behind focusing on ASOs for treating rare diseases

28:03 Building EveryONE Medicines and Kent’s approach to leadership

33:20 Lessons from Kent’s career

37:17 Closing remarks 

Find out more

• EveryONE Medicines (https://www.eomeds.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Matt Burgess, genetic counselor, host of the Demystifying Genetics podcast, and Adjunct Professor at Bay Path University. They discuss the evolution of genetic counseling, ethical challenges in gene therapy, and Matt’s experiences with his podcast.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Matt

02:09 Matt’s run-ins with Olivia Newton John while working at Austin Hospital in Melbourne

04:34 Matt’s background and path to genetic counseling 

06:58 The evolution of the field of genetic counseling over time and the role of counselors

12:47 Matt’s work on rare disease AP-4 hereditary spastic paraplegia (AP-4-HSP) and the ethical considerations of gene therapy

20:22 Balancing the needs and expectations of individuals and families in counseling 

23:06 Rebranding negative connotations of the word “counseling” 

26:58 Memorable episodes from Matt’s podcast Demystifying Genetics

34:31 Differences in genetic counseling and healthcare in the US versus Australia and the UK

40:00 Matt’s current work on writing a novel, starting a company called Rosalind Genetics, and being involved in genetic education

42:47 The potential and drawbacks of AI models in the context of genetic counseling and information

46:46 Closing remarks

Find out more

• Demystifying Genetics (https://demystifying-genetics.buzzsprout.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Salvador Rico, Chief Medical Officer at Encoded Therapeutics. They discuss Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and fundamental challenges and exciting advances in the genetics field.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Salvador and how he became involved in drug development

11:01 Frustrations and rewards of the genetics field

13:59 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)

19:46 Risk of liver issues in gene therapy trials and attempts to mitigate them

24:22 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team

27:22 Steps towards therapeutic targeting of gene regulatory elements 

30:04 Advantages of different methods for drug delivery 

32:31 DNA- versus RNA-based therapy

34:56 Insights from approaches in other fields, including psychiatry

36:35 Considerations for using natural history studies

40:32 Expectations and goals for Encoded Therapeutics’ current and upcoming studies

43:17 Closing remarks

Find out more

• Encoded Therapeutics (https://encoded.com/)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Leeland Ekstrom, CEO and co-founder of Nashville Bio. They discuss how Leeland went from being a consultant on a project for Vanderbilt University to a co-founder of a start-up and the unique aspects of NashBio’s clinical and genetic database.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Leeland and the origin story of Nashville Bio

05:13 Process of setting up NashBio’s genome resource with 250K individuals

11:52 How different pharmaceutical companies responded to NashBio’s database and its unique advantages compared to others

17:50 Key priorities for applications of the resource beyond target discovery

20:19 The process of selecting additional gaps that NashBio’s services can fill versus letting others fill them

25:02 Advantages at Vanderbilt Medical Center that facilitated the project and how it can be replicated at other centers

30:32 Immediate and long-term impacts of current NIH funding cuts on biotech and academia

36:43 NashBio’s current major focuses and future goals

39:20 Closing remarks

Find out more

• NashBio (https://nashbio.com/)

• Press release: Alliance for Genomic Discovery completes 250,000 whole genomes to accelerate drug discovery (https://www.illumina.com/company/news-center/press-releases/press-release-details.html?newsid=b4b0c901-f8a2-4802-a4ef-b81167e24cfe) 

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link