Clinical Ethics at the Crossroads of Genetic and Reproductive Technologies

Chapter 1: Genomic editing: From human health to the “perfect child”

• • 1. Introduction
• • 1.1 Beginnings
• • 1.2 Definitions and context
• • 1.3 Recombinant DNA technology: The basis for DNA modification
• • 1.4 Genome editing
• • 1.5 Zinc finger nucleases (ZFNs)
• • 1.6 CRISPR/Cas9 technology
• • 1.7 Base editing technology
• • 1.8 Principles of using genome editing in research and clinical practice
• • 2. Ethical issues in clinical genome editing
• • 2.1 Nonmaleficence and risk/benefit assessment
• • 2.2 Beneficence in gene editing therapies
• • 2.3 Respect for autonomy
• • 2.4 Confidentiality
• • 2.5 Applying the principle of justice in clinical genome editing
• • 2.6 Eugenics, enhancement, and “designer babies”
• • 3. Conclusions
• • References

Chapter 2: Ethics of mitochondrial gene replacement therapy

• • 1. Introduction
• • 2. What is mitochondrial disease and mitochondrial donation?
• • 3. The UK timeline
• • 4. The international position
• • 5. Are the techniques safe?
• • 6. Ethical issues
• • 7. “Three parent babies” and identity
• • 8. Genetic modification and the “slippery slope”
• • 9. Risks for egg donors
• • 10. Ethical differences between PNT and MST
• • 11. Mitochondrial disease as complex: Diagnosis, predicting risk, and genetic counseling
• • 12. Alternative reproductive options
• • 13. Polar body transfer and gene editing
• • 14. Conclusion
• • References

Chapter 3: Reproductive technologies used by same-gender couples

• • 1. Introduction
• • 2. Procreative autonomy
• • 3. Gamete and embryo donation
• • 4. Surrogacy agreement
• • 5. Trans parenthood
• • 6. Conscience clause
• • 7. Conclusions
• • References
• • Further Reading

Chapter 4: Ethical issues raised by multiparents

• • 1. Introduction
• • 1.1 Key terms of the debate: Filiation, kinship, and parenthood
• • 2. Multiparents of children born through ARTs
• • 2.1 Maternity
• • 2.2 Paternity
• • 3. Where do all these parents come from?
• • 3.1 Sperm donation
• • 3.2 Egg donation
• • 3.3 Embryo donation
• • 3.4 Surrogacy
• • 4. Ethical issues
• • 4.1 The right to know one’s origins
• • 4.2 Donors’ anonymity
• • 4.3 The consent of participants
• • 5. Secondary ethical issues
• • 5.1 Medical tourism
• • 5.2 Slippery slope
• • 6. Final considerations
• • References

Chapter 5: Revisiting the nondirective principle of genetic counseling in prenatal screening

• • 1. Introduction
• • 2. Genetic counseling: An overview
• • 3. The nondirective principle in genetic counseling
• • 3.1 “Nondirectivity” or “sharing decision-making”?
• • 3.2 The nondirective principle of genetic counseling in preimplantation screening
• • 3.3 The nondirective principle of genetic counseling in prenatal screening
• • 4. Does the nondirective principle compromise genetic counseling in prenatal screening?
• • 5. Does genetic counseling in prenatal screening compromise the nondirective principle?
• • 6. The concept of nondirectivity vs the role of genetic counseling
• • 7. Activating the conscience clause in genetic counseling in prenatal screening?
• • 8. Genetic counseling in prenatal screening in ethnic and cultural minorities
• • 9. Medical tourism for abortion after genetic counseling
• • 10. Issues of genetic counseling in prenatal screening
• • 10.1 The absence of genetic counseling
• • 10.2 The inappropriate genetic counseling
• • 11. Final considerations
• • References

Chapter 6: Sex selection, gender selection, and sexism

• • 1. Introduction
• • 2. The roots and reasons for sex selection
• • 3. From politics on reproduction to biopolicy
• • 4. Missing girls: Why and how many?
• • 5. Legal and ethical questions
• • 6. Conclusion
• • References

Chapter 7: The impact of Big Data on beginning-of-life issues

• • 1. Introduction: First, what is really “Big Data”?
• • 2. Big Data and healthcare: An expanding universe
• • 3. Big Data and Beginning-of-life issues: A field in its infancy
• • 4. Conclusion: Work in progress
• • References

Chapter 8: The moral status of the embryo and its uses: Bioethics and social perceptions

• • 1. Introduction
• • 2. The empirical perspective in bioethics and public perceptions of science studies
• • 3. The notion of moral status
• • 4. Contrasting narratives on the moral status of the embryo
• • 5. The status of the embryo frame and the beginning of individual human life
• • 6. Views on the status of the embryo, religious beliefs, scientific literacy, and gender
• • 7. Moral status and attitudes to embryo research
• • 8. Conclusions
• • References

Chapter 9: Fetal reduction

• • 1. Bioethical issues of fetal reduction: Why words matter
• • 1.1 Medical use: Selective fetal reduction
• • 1.2 Medical use: Nonselective fetal reduction
• • 1.3 Nonmedical uses: Selective fetal reduction
• • 1.4 Nonmedical use: Nonselective fetal reduction
• • 2. The moral status of embryo and fetus
• • 3. Fetal reduction: “A soft cover for hard choices”
• • 4. Parental autonomy and parental responsibility
• • 5. Conclusion
• • References

Chapter 10: Stem cell therapies for neurodegenerative disorders: An ethical analysis

• • 1. Introduction
• • 2. An overview on stem cell therapies for neurodegenerative disorders
• • 2.1 Parkinson’s disease
• • 2.2 Stem cell treatments for other neurological disorders
• • 2.3 Use of placebo controls in sham surgery
• • 3. Risk-to-benefit analysis for stem cell therapies in neurodegenerative disorders
• • 3.1 What are the potential benefits of stem cell therapy in neurodegenerative disorders?
• • 4. Induced pluripotent stem cell therapies for neurodegenerative disorders
• • 5. Moral status of IPSCs
• • 6. Conclusions
• • References

Chapter 11: Predictive genetic testing in multifactorial disorders

• • 1. Introduction
• • 2. Respect for autonomy
• • 2.1 Delivering relevant information
• • 2.2 Understanding relevant information
• • 2.3 Capacity to act voluntarily
• • 2.4 The concept of relational autonomy in predictive genetic testing
• • 3. Nondirectiveness in predictive testing for multifactorial disorders
• • 4. Direct-to-consumer genetic testing
• • 5. When to recommend predictive genetic testing?
• • 6. Nonmaleficence and risk assessment
• • 7. Confidentiality and family sharing of the genetic results
• • 8. Predictive genetic testing in children
• • 9. Genetic exceptionalism and multifactorial disorders
• • 10. Conclusions
• • References

Chapter 12: Whole-genome sequencing as a method of prenatal genetic diagnosis

• • 1. Introduction
• • 2. From the standard of prenatal diagnosis to whole-genome sequencing
• • 3. Whole-genome sequencing as a prenatal diagnostic tool
• • 3.1 What is whole-genome sequencing?
• • 3.2 Whole-genome sequencing applications in prenatal diagnosis
• • 3.3 Limitations of whole-genome sequencing
• • 4. Ethical problems surrounding whole-genome sequencing
• • 4.1 Large amounts of information
• • 4.2 Anxiety and confusion in parents
• • 4.3 Parents’ reproductive choices, expectations, and genetic determinism
• • 4.4 Right of the parents to information vs right of the child to “Not to Know”
• • 5. The importance of pre-WGS test and post-WGS diagnostic counseling
• • 5.1 Counseling in WGS
• • 5.2 Pre-WGS test counseling
• • 5.3 Post-WGS diagnostic counseling
• • 5.4 Ethical reflection on WGS test in prenatal diagnosis
• • 6. Conclusion
• • References

Chapter 13: Noninvasive prenatal genetic diagnosis

• • 1. Introduction
• • 2. High- versus low-risk populations
• • 3. Reproductive autonomy
• • 4. Counseling for NIPT
• • 5. Should parents be allowed to get tested “for information only”
• • 5.1 A teleological approach to NIPT
• • 6. NIPT and discrimination
• • 7. Eugenics, procreative beneficence, and NIPT
• • 8. Conclusions
• • References

Chapter 14: Prenatal testing in low-risk populations: After routinization for aneuploidy

• • 1. Introduction
• • 2. Background on offering the test to low-risk women
• • 3. Diagnostic test versus screening test
• • 4. Reduced penetrance and variable expressivity
• • 5. Negative test and healthy baby assumptions
• • 6. Incidental findings: Maternal conditions
• • 7. Ethics of testing just for information
• • 8. Practical issues: Who will counsel patients?
• • 9. OB/Gyn counseling
• • 10. Information access outside of the United States
• • 11. Problematic solutions
• • 12. Linear model of information transmission
• • 13. Justice issues: Access to testing
• • 14. Conclusion
• • References

Chapter 15: Using genetics for enhancement (liberal eugenics)

• • 1. Introduction
• • 1.1 Definition of enhancement
• • 1.2 Types of enhancement
• • 1.3 (How) should we distinguish enhancement from therapy?
• • 2. Genetic enhancement
• • 2.1 Genomics and epigenomics as base for genetic enhancement
• • 2.2 High-throughput methodology for genome wide genetic, epigenetic, and gene expression profiling
• • 2.3 Personalized medicine as a model for implementation of genetic enhancement
• • 2.4 From predictive genomics to preventive medicine and genetic enhancement
• • 2.5 Ethical issues in personalized medicine
• • 2.6 Gene therapy, molecular-targeted therapy, and cellular therapy
• • 2.7 Ethical aspects of gene therapy, molecular-targeted therapy, and cellular therapy
• • 2.8 Gene enhancement, molecular-targeted enhancement, cellular enhancement
• • 3. Liberal eugenics
• • 4. Regulation, health coverage, and public opinion
• • 5. Conclusion
• • Acknowledgments
• • References

Chapter 16: Should incidental findings arising from prenatal testing be reported indiscriminately to patients?

• • 1. Introduction
• • 2. Incidental findings in the prenatal setting
• • 2.1 Challenges of definition
• • 2.2 Current practice, new developments, and specific features of the prenatal setting
• • 3. Reporting incidental findings in the prenatal setting
• • 3.1 Arguments pro disclosure
• • 3.2 Arguments against disclosure
• • 4. Handling incidental findings: Informed consent procedures and pretest counseling in genetic testing
• • 5. Conclusion
• • References

Chapter 17: Third-party sharing of genetic information

• • 1. Introduction
• • 2. Disclosure of genetic data to relatives
• • 2.1 Disclosure of genetic information by the patients to their biological relatives
• • 2.2 Communication by parents of genetic information about their children
• • 2.3 Refusal of the individuals to disclose genetic data to their biological relatives
• • 2.4 Disclosure of information by the healthcare provider without the patient’s consent
• • 3. Disclosure of genetic information to employers
• • 4. Disclosure of genetic data to health insurance companies
• • 5. Third-party sharing of genetic data in the context of biomedical research
• • 5.1 Sharing data resulting from genetic testing with research entities
• • 5.2 Disclosure of genetic data resulting from research to the participants’ relatives
• • 6. Disclosure of data resulting from DTC genetic tests
• • 7. Disclosure of data resulting from genetic interpretation services
• • 8. Third-party sharing for forensic purposes
• • References

Chapter 18: Cerebral and noncerebral organoids

• • 1. Stem cells applications: Organoids and brain organoids
• • 1.1 Biological foundations
• • 1.2 Brain organoids: What they are and what they recapitulate of the human brain
• • 1.3 Applications and limitations
• • 2. Ethical issues
• • 2.1 Cell origins, biobanking, and usage of brain organoids
• • 2.2 Nonhuman animals and grafted organoids
• • 2.3 Consciousness and moral status
• • 3. Final remarks
• • 3.1 Brain organoids and society
• • 3.2 Conclusions
• • References

Chapter 19: Cognitive enhancement: Bioethical aspects

• • 1. Introduction
• • 2. Libertarian and utilitarian theories
• • 3. Personalist and egalitarian theories
• • 4. Hidden risks of enhancement
• • 5. Possible future regulation about enhancement
• • 6. Conclusion
• • References

Chapter 20: Risks and benefits of direct-to-consumer genetic testing in the reproductive context

• • 1. Introduction
• • 2. A brief history of DTC genetic testing
• • 3. Current status of DTC genetic testing relevant to reproductive decisions
• • 3.1 Physician involvement
• • 3.2 DTC genomic platforms
• • 3.3 Types of results provided
• • 3.4 Concerns currently raised
• • 4. Limits and risks
• • 4.1 Limitation in detectable genes and variants
• • 4.2 Variants of unknown significance
• • 4.3 Accuracy (false positives and false negatives)
• • 4.4 Varying interpretation
• • 4.5 Risks of raw data interpretation
• • 4.6 Privacy risks
• • 5. Benefits
• • 6. Ethical issues
• • 6.1 Principlism approach to DTC genetic testing
• • 6.2 Ethical challenges in DTC-based reproductive choices
• • 7. Conclusion
• • References

Chapter 21: Genetic immunization: Enhancement or public health measure?

• • 1. Introduction
• • 1.1 Definitions and background
• • 1.2 Introducing a case study
• • 2. Public health and ethics
• • 2.1 Definition and goals
• • 3. Moral concepts from public health ethics
• • 3.1 Collective easy rescue
• • 3.2 Public goods
• • 3.3 Collective welfare
• • 3.4 Distributive justice
• • 4. Ethical analysis of genetic immunization
• • 4.1 Stakeholders, harms and benefits
• • 4.2 Distribution of stakeholder harms and benefits
• • 4.3 Policy alternatives
• • 5. Conclusions
• • References