Can we stop genetic diseases before birth?

Key Concepts

• Pre-implantation Genetic Testing (PGT)
• In Vitro Fertilization (IVF)
• Monogenic Diseases
• Polygenic Diseases
• Genetic Risk Scores
• Relative Risk vs. Absolute Risk
• Ethical Considerations of Embryo Screening

Orchid's Approach to Embryo Screening

• Mission: To help IVF patients make informed decisions about their babies' health by testing embryos before pregnancy. Founded by Noor Siddiqui, inspired by her mother's genetic disease-induced vision loss.
• Current Limitations of Embryo Testing: Existing tests analyze only about 1% of the DNA.
• Orchid's Technology: Reads the entire genome of an embryo.
  • Requires only five cells from a day-five embryo (approximately 125 cells total).
  • Developed a new amplification protocol and computational pipeline to work with the limited DNA in the sample (10,000 times less than blood or saliva).
• Cost: $2,500 per embryo (compared to $4,000-$12,000 for standard pre-implantation genetic testing).
• Types of Diseases Screened:
  • Monogenic Diseases: Caused by a mutation in a single gene. Orchid screens for over 1,200 monogenic conditions, including birth defects, pediatric cancers, and genetic forms of autism like Rett syndrome.
  • Polygenic Diseases: Triggered by a combination of gene mutations, environmental factors, and chromosome damage. Orchid uses genetic risk scores built from large datasets (millions of individuals) to quantify genetic risk precisely.

Orchid's Laboratory Process (Durham, North Carolina)

• Sample Handling:
  • Embryo samples are received and frozen.
  • Samples are accessioned (registered).
• Quality Control: Scientists check for the correct number of chromosomes.
• DNA Extraction and Amplification: DNA is extracted and amplified to analyze genetic variations.
• Sequencing: DNA is sequenced with 99% accuracy.
• Inheritance Analysis: Saliva samples from parents are collected to determine if variations are inherited from the mother or father.
• Turnaround Time: The entire process takes 2-3 weeks.
• Results Delivery: Genetic counselors deliver results to patients and their clinical teams to aid in embryo selection.

Ethical Considerations and Concerns (Robert Klitzman, Columbia University)

• Cost and Accessibility: IVF and embryo screening are expensive and often not covered by insurance, potentially creating disparities in access.
  • Example: Breast cancer could become more prevalent among lower socioeconomic groups if wealthier individuals screen out breast cancer mutations through IVF.
• Informed Decision-Making: Concerns about whether people fully understand the implications of the tests.
• Misinterpretation of Risk: Companies may overemphasize relative risk without providing adequate context about absolute risk.
  • Example: Doubling the risk of schizophrenia from 1% to 2% (relative risk) still leaves a 98% chance of not developing the condition (absolute risk).
• Coercion: Noor Siddiqui emphasizes that no one should be coerced into using IVF or Orchid's services.

Noor Siddiqui's Perspective

• Believes the purpose of science and medicine is to reduce suffering.
• Sees embryo screening as a way to avoid catastrophic health outcomes.
• Predicts that this technology will reshape how people have children.

Synthesis/Conclusion

Orchid is pioneering comprehensive embryo screening using advanced genomic sequencing and computational analysis to identify monogenic and polygenic disease risks. While this technology offers the potential to reduce the incidence of inherited diseases and improve health outcomes, it also raises significant ethical concerns regarding cost, access, informed consent, and the potential for misinterpreting genetic risk. The future of genetic tools in reproductive care hinges on navigating these ethical issues responsibly.