Genetic Research for Disease Resilience

Aug 3, 2024

Lecture on Genetic Research and Disease Prevention

Introduction

  • Speaker's Background: Oncology at Children's Hospital in Philadelphia.
  • Key Moment: Encountered a father and son with inherited eye tumor, retinoblastoma.
  • Impact: Led to discovery of the first cancer susceptibility gene.

Advances in Genetic Understanding

  • Seismic Shift: Significant advances in understanding genetic variations behind diseases over the past decades.
  • Current Reality: While diagnostics have improved, drug development efficiency remains stagnant.

Challenges in Drug Development

  • Early Stage: Still learning the genetic code, unable to fully read and understand it.
  • Loss of Function: Most genetic changes are loss of function, hard to develop drugs to restore function.

Proposed Shift in Focus

  • Current Focus: Studying the sick and listing altered components.
  • New Idea: Study those who stay well despite having genetic risks for diseases.
    • Look for individuals who are genetically predisposed to diseases but show no symptoms.

Feasibility Examples

  • HIV and AIDS (1980s-1990s): Some individuals did not get AIDS despite high HIV levels due to protective mutations.
  • High Lipid Levels and Heart Disease: Research by Helen Hobbs identified protective mutations in individuals with high lipid levels who did not get heart disease.

The Resilience Project

  • Objective: Find individuals with genetic factors that protect against diseases.
  • Methodology: Systematic approach to study all childhood inherited diseases with severe symptoms and known genetic alterations.
  • Global Search: Include diverse populations, aiming to study one million individuals.

Technological and Collaborative Advances

  • Cost Reduction: Significant drop in data generation and analysis costs.
  • Advanced Tools: New tools in network biology and systems biology.
  • Collaborative Effort: Researchers and institutions willing to join the open, crowd-sourced project.

Progress and Results

  • Screening Key: Developed a key for decoding resilience factors.
  • Sample Collection: Collaboration with various institutions yielded over 500,000 samples.
  • Findings: Dozens of strong candidate 'unexpected heroes' identified.

Future Directions

  • Beta Phase Launch: Seeking prospective individuals for further study.
  • Public Involvement: Need public engagement and participation for success.
  • Long-term Goal: Extend research to adult diseases like Alzheimer's and Parkinson's.
  • Open-Source Approach: Encourage sharing and collaboration for broader impact.

Conclusion

  • Call to Action: Encouraging individuals to participate and share their genetic information.
  • Vision: Evolving from current resource constraints to designing preventive therapies through collective effort.

Thank you.

(Applause)