Week 7.2 Prenatal Genetic Testing and Stem Cell Research

Recap: Prenatal Genetic Testing and Models of Disability

• Core Perspective: Perspectives on In Vitro Fertilization (IVF) and Preimplantation Genetic Testing (PGT) apply to the broader context of prenatal genetic testing.

• Disability Models:

  • Medical Model: Frames disability (e.g., deafness or hearing loss) as a medical problem to be "cured" or solved through biomedical intervention.

  • Social Model: Frames disability as a unique community-based cultural factor or a social construction requiring societal accommodation and structural changes rather than individual medical fixes.

Case Study: The Deaf Community and Genetic Testing

• The Middleton Study: A survey conducted with approximately $87$ individuals, categorized as:

  • Culturally deaf (identified as "Big D" Deaf).

  • Non-culturally deaf or hearing individuals.

• Survey Findings:

  • Testing Preference: The majority of participants were opposed to genetic testing for deafness for themselves.

  • Child Preference: While some preferred hearing children and a minority preferred deaf children, the majority stated "it doesn't matter."

  • General Sentiment: Approximately $83\%$ of the class identified that the community is generally skeptical about the value and implications of such testing.

• Big D Deaf Culture: This community views deafness as a unique cultural identity rather than a medical pathology.

• Engagement Demands: Culturally deaf individuals desire greater involvement in the design and implementation of research that affects them, emphasizing community autonomy and the inclusion of community members as active researchers.

• Selection for Deafness: There are documented instances of deaf individuals seeking IVF and PGD to specifically select for deaf embryos (e.g., choosing a deaf sperm/egg donor) to embrace their culture. This creates significant tension with the medical model of disability and traditional bioethics.

Disability Determinism and Critical Perspectives

• Rosemary Garland Thompson: Focuses on disability as a cultural narrative and social construction.

• Definition of Disability Determinism: Per Garland Thompson, this is the idea that "suffering, disadvantage, loss, and failure are destiny for people with disabilities, whereas a non-disabled life is imagined to be free of such contingencies."

• The Six Truths (Garland Thompson):

  1. All human beings need care, assistance, and a sustaining environment to live.

  2. Disability disadvantage results from living in an unaccommodating environment.

  3. Quality of life cannot be predicted in advance.

  4. Disability can produce life advantages.

  5. What counts as disability changes over time and space.

  6. The border between disabled and non-disabled shifts over a lifetime.

• Impact of Technology (Allison Meyer): The existence of a test (e.g., for Down syndrome) can change the meaning of the condition. As testing becomes routine, the condition being tested for becomes "ever more dreaded, ever more unthinkable."

• The IQ Parallel: The existence of IQ tests and their subsequent rankings implies a value judgment (social creation) that higher intelligence is inherently "better."

Complexities of Reproductve Choice

• Social Expectations: While testing like NIPT is voluntary, it is socially expected and recommended by guidelines (e.g., ACOG $2020$ guidelines for aneuploidy).

• Knight and Miller (1998): Research published in Hypatia notes that medical providers may reinforce the medical model by:

  • Providing inadequate information during informed consent.

  • Focusing solely on medical aspects and ignoring the lived social experience of disability.

  • Actively counseling patients toward termination after a positive diagnosis for Down syndrome.

• Relational Autonomy: A feminist bioethical framework emphasizing that choices are not made in a vacuum but are influenced by political institutions, kinship networks, and cultural norms. True autonomy requires the redesign of social and material environments to support whatever choice a person makes.

• The Eugenics Critique:

  • Some argue prenatal testing is eugenic due to high rates of selective termination for Down syndrome across many countries.

  • Distinction exists between historical state-mandated eugenics and "contemporary eugenics" driven by social expectations and lack of support for the disabled.

Introduction to Stem Cell Biology

• Definition of a Stem Cell: A cell with three main properties:

  1. Indefinite Reproduction: Can replicate itself many times over (similar to HeLa cells).

  2. Unspecialized/Undifferentiated: Acts as a "blank slate" or generic cell.

  3. Capacity to Differentiate: Can develop into specialized cells (e.g., neurons, muscle fibers, red blood cells) under specific conditions.

• Potency Classes:

  • Pluripotent: Can become almost any cell in the organism (e.g., Embryonic Stem Cells).

  • Multipotent: Can become several different kinds of cells but are restricted to a specific lineage (e.g., Somatic/Adult stem cells like bone marrow).

Types of Stem Cells and Therapies

• Embryonic Stem Cells (ESCs):

  • Derived from the inner cell mass of a blastocyst (early-stage embryo, approximately $5$ to $7$ days old).

  • Benefits: Easier to grow in culture, divide indefinitely, and are pluripotent.

  • Downsides: Risk of transplant rejection and high ethical controversy.

• Somatic (Adult) Stem Cells:

  • Found in tissues like bone marrow, adipose tissue, gut lining, and dental pulp.

  • Example: Bone marrow transplants are used to treat blood cancers by replacing a patient's immune system.

• Transplant Categories:

  • Allogeneic: Getting stem cells from another person (requires immune matching).

  • Autologous: Getting stem cells from oneself (e.g., collecting bone marrow before chemotherapy and re-infusing it later).

• Induced Pluripotent Stem Cells (iPSCs):

  • First accomplished in humans in approximately $2007$.

  • A fully differentiated cell (like a skin cell) is treated with regulatory genes to reverse it to an undifferentiated pluripotent state.

  • Allows for personalized, autologous treatments that match the patient's genome perfectly, avoiding rejection.

Regulation and Ethics of Human Embryonic Stem Cell Research

• The Dickey-Wicker Amendment (1995): Banned the use of federal (NIH) funds for the creation of human embryos for research or for research in which an embryo is destroyed.

• Policy Nuance: Researchers often use state funds (like in California) to create cell lines and then use federal funds to study the lines once created, creating a strictly partitioned funding environment.

• The 14-Day Rule: A regulation stating that human embryos cannot be allowed to develop in a lab culture for longer than $14$ days.

• The Compromise: Most ESC lines used in the US come from excess or non-viable embryos donated with informed consent from IVF clinics. They cannot be created solely for research purposes using federal funds.

• Clinical Reality: Currently, there are no FDA-approved therapies derived from human embryonic stem cells, though many trials are ongoing (e.g., treatments for Macular Degeneration using iPSC cells).

Ethical Framework: Hard vs. Soft Impacts

• Hard Impacts: Physical, quantifiable, or easily measurable effects.

  • Example: The risk of tumor formation (cancer) because stem cells divide rapidly and can accumulate genetic variations.

• Soft Impacts: Less tangible, qualitative effects on social structures and ethical perceptions.

  • Example: How stem cell research might change perspectives on using animals in research if human-based dishes can model diseases instead.

Slide Notes:

Disability determinism: suffering, disadvantage, loss, and failure are destiny for people with disabilities, whereas a nondisabled life is imagined to be free of such contingencies

Stem cells:

• reproduce itself indefinitely

• is unspecialized

• under appropriate conditions, can differentiate into specialized cell types

Two stem cell categories: somatic and embryonic

Embryonic stem cells

• become any cell in the body

• large numbers easily grown in culture

• can cause transplant rejection

• virtually immortal

Adult Stem cells:

• limited in what it can differentiate into

• rare in mature tissues and not easy to grow in culture

• patients own cells used so no transplant rejection

• finite life span

Dickey-Wicker Amendment stands: illegal to use federal funds to create stem cells lines from embryos (must use other funds)

• May use spare embryos from an IVF treatment but not created for research

• Informed consent required to use IVF embryos

• Use only for studies with major scientific value that cannot be attained by other means