Tomorrow's Cure: “Shortening the Diagnostic Journey: Genomics for Every Child”

Podcast: Tomorrow's Cure (Mayo Clinic)
Episode Date: February 25, 2026
Host: Kathy Werzer
Guests:

• Dr. Whitney Thompson, Mayo Clinic (genomics, ethics, NICU)
• Dr. Stephen Kingsmore, CEO/President, Rady Children’s Institute for Genomic Medicine
• Sean George, CEO, Inflection Medicine

Overview

This episode delves into how whole genome sequencing, advanced therapeutics, and artificial intelligence are transforming the diagnosis and treatment of rare genetic diseases in children—especially in neonatal intensive care units (NICU). The discussion centers on shifting from a long, painful “diagnostic odyssey” to rapid, precise, and potentially lifesaving answers for children and families, with stories of hope, practical insights, and a look at how these approaches can be democratized and scaled to reach every child.

Key Discussion Points & Insights

1. The Diagnostic Odyssey and Why It Matters

[02:03-03:39]

• Definition: The “diagnostic odyssey” is the long, often years-long process families endure seeking answers for rare diseases.
• Prevalence: Around 300 million people have a rare disease; about half are children.
• Big Problem: Most rare diseases are genetic, but patients are often misdiagnosed with more common conditions.
• Quote:

  “The diagnostic odyssey is because in general, the medical profession is really bad at detecting these diseases.”
  — Dr. Kingsmore [02:29]

2. The Shift to Genomic Medicine in NICUs

[03:48-05:49]

• Past approach: Stepwise genetic testing with limited answers and delays.
• New paradigm: Rapid whole genome sequencing as initial, comprehensive test—can deliver critical diagnosis within days.
• At Mayo Clinic, this is now standard care for qualifying NICU patients, but not so in most centers globally or even nationally.
• Quote:

  “Now...we send what we call rapid whole genome sequencing, one comprehensive rapid test that can look at all of the genes that we know currently to cause disease and hopefully find an answer for families.”
  — Dr. Thompson [03:48]

3. The Global (and National) Landscape

[05:03-05:49]

• Only a few dozen centers worldwide regularly use rapid sequencing in infants.
• Mission of the guests: Make rapid genome sequencing the universal standard of care.
• Quote:

  “There’s no reason not to, other than just a momentum shift.”
  — Dr. Kingsmore [05:03]

4. The Impact and Frustration of Genomics Implementation

[05:53-07:49]

• Sean George: Lifelong genomics advocate; progress has been exciting yet, “it’s been a frustrating career” due to slow adoption.
• Inflection Medicine is building platforms to democratize access, making sequencing available and actionable even outside cutting-edge centers.

5. Complexity and Promise of Genomic Discoveries

[08:07-10:45]

• Genetic disorders are more diverse and complex than previously thought—what we call a “disease” like autism or sudden infant death is actually many different genetic diseases with overlapping symptoms.
• Technological advances now allow for decoding an individual’s genetic blueprint quickly and inexpensively.
• Quote:

  “If you go back 20 years, it would seem like magic how quickly and effectively and inexpensively we can get three gigabases of information, all of which is starting to be decoded.”
  — Sean George [09:17]

6. Artificial Intelligence in Genomic Medicine

[10:45-13:48]

• AI is employed to interpret complex genome data and identify potential therapies (drug repurposing, personalized solutions).
• Example: Babyforce initiative at Mayo Clinic uses AI (NIH Translator) to match genetic variants to existing drugs; therapies are then tested in patient-derived cells and moved rapidly to clinical use for that child.
• Case Study:
  • Jori: Diagnosed in infancy with deSanto-Shinawi syndrome via rapid sequencing. AI identified a drug that, when tested in her cells, increased required gene function; subsequent treatment led to dramatic developmental improvements.
  • Quote:

    “Within the first month of starting that treatment, she started walking, she started talking…far beyond what we would have expected.”
    — Dr. Thompson [13:31]

7. AI and Genomics at Scale—Other Success Stories

[13:55-17:10]

• Connor: Teenage boy misdiagnosed for years, finally identified via genomic sequencing as having a rare genetic epilepsy. A bespoke RNA therapeutic was developed to selectively silence the faulty gene; post-treatment, he became seizure-free and made developmental gains.
• The approach—using “N of 1” personalized medicine—eliminates much of historical risk and time in therapeutic development.
• Quote:

  “When you have developmental loss, that’s supposed to be irreversible. These little kids—they’re defying that.”
  — Dr. Kingsmore [16:33]

8. Economics and Scaling: Cost and Policy Barriers

[17:52-19:55], [21:13-23:23]

• Upfront cost of individualized therapies can be high, but rapid diagnosis saves tens of thousands per patient vs. prolonged testing and hospital stays.
• As technologies mature, costs will drop by “two orders, three orders of magnitude.”
• National policy is critical: Some states like California have legislated Medicaid coverage for rapid sequencing (e.g., Project Baby Bear/Deer). 20+ states now cover this; NHS in England is moving ahead as well.
• Quote:

  “The cost avoidance by simply reading the book and understanding what to do is immense.”
  — Sean George [17:58]

9. From “N of 1” to “N of Many”: The Challenge of Democratizing

[21:13-27:24]

• How can success with individual kids be extended to broader disease communities?
• Centers of excellence will likely lead specialized therapy development, but universal neonatal rapid sequencing can (and should) be scaled everywhere.
• Need for platforms that move diagnostics and resultant treatments out to everyday practitioners and patients.
• Quote:

  “There will be a day where we will look back and think to ourselves, how did we possibly practice medicine without understanding…the blueprint was right there…and we weren’t using it.”
  — Sean George [27:24]

10. Future Hopes: Scaling & Collaboration

[29:00-31:44]

• Scaling personalized therapy (“From N of 1 to N of Many”) is a central focus: automating and accelerating every step from genetic diagnosis to therapy delivery.
• AI, automation, and institutional partnerships are key.
• The collective hope is making the entire diagnosis-to-therapy process so “any NICU” (and eventually all pediatric practices) can do it smoothly.

Memorable Moments & Notable Quotes

• “The diagnostic odyssey is…completely needless.”
  — Dr. Kingsmore [02:29]
• “When you have developmental loss, that’s supposed to be irreversible. Well, these little kids…they’re defying that.”
  — Dr. Kingsmore [16:33]
• “I want [this tool] for clinicians and patients everywhere.”
  — Dr. Thompson [26:50]
• “How did we possibly practice medicine without understanding…the blueprint was right there…and we weren’t using it.”
  — Sean George [27:24]
• “The biggest ethics violation that we are collectively…performing right now is not using this information when it’s available. These kids’ lives could be dramatically improved and we’re not using it to the full extent.”
  — Sean George [32:43]

Practical Experience: Policy and Implementation

[23:23-26:47]

• Project Baby Bear: $2M state project in CA; rapid sequencing for Medicaid babies, solved 40% of cases, saved $2M in hospitalization costs.
• Led to Medicaid policy; similar projects and state policies are scaling up.
• Internationally, the NHS UK is ahead with national sequencing policy.

Ethical and Societal Considerations

[33:59-35:56]

• Rights to privacy, personal autonomy, access to therapies must be guarded.
• Recognize that “the patient–doctor relationship is now two individuals having a conversation,” marking a shift from the earlier paternalistic model.

Guests’ Motivations

[36:19-39:28]

• Dr. Thompson: The dramatic and increasing hope from rapid advances and individual success stories (“stories like Baby Jory”).
• Sean George: Personal family history, desire to end the era of endless searching for answers for families.
• Dr. Kingsmore: Personal connection (grand niece Heidi) and commitment to expanding access and therapies globally.

Key Timestamps

| Timestamp | Segment | |-------------|-------------------------------------------------------------------------------| | 02:03–03:39 | What is the “diagnostic odyssey” for rare disease families? | | 03:48–05:03 | The paradigm shift: rapid genome sequencing in the NICU | | 05:49–07:49 | The technological gap and Inflection Medicine’s mission | | 08:07–10:45 | Complexity and revolutionary changes in the field of genomic medicine | | 10:45–13:48 | AI, drug repurposing, and transformative patient stories (Jori) | | 13:55–17:10 | AI-assisted personalized therapy (Connor) and therapeutic platforms | | 17:52–19:55 | Economic benefits and the scaling potential of rapid genomics | | 23:23–25:17 | Policy experiments: Project Baby Bear and new Medicaid coverage | | 27:24–27:54 | The future: how will we look back at this era of medicine? | | 33:59–35:56 | Ethics: Patient rights, privacy, and shifting medical paradigms | | 36:19–39:28 | Guests’ inspirations and personal stories | | 29:00–31:44 | Next steps: scaling, trials, and automation (Babyforce and beyond) |

Takeaways

• The “diagnostic odyssey” is becoming obsolete—science, policy, and AI are aligning to provide rapid, actionable diagnoses for sick children, but the goal is universal global access.
• Personalized, AI-assisted therapy is now possible—from drug repurposing to bespoke RNA treatments, stories demonstrate remarkable outcomes in children with previously untreatable genetic disorders.
• Scaling and equity are the next frontiers—spreading not just the diagnostic technology but also new therapeutics to all patients regardless of geography or hospital system is both a technical and moral imperative.
• Ethics and regulation require careful guidance—especially regarding data privacy and ensuring access for all children, not just those at elite centers.
• The field is moving fast—faster than ever—and the experts agree: we’re at an inflection point where today’s miracles will be tomorrow’s standard care.

This episode is an inspiring look at how the integration of genome sequencing, AI, and collaborative care is already changing lives today—and how, with continued innovation and commitment, it could soon end the long, painful search for answers that so many families still endure.