Public Comment: Clinical Use of Human Germline Genome Editing: Responses to the Public Call for Evidence
Final Responses Submitted to the Public Call for Evidence from the
International Commission on the Clinical Use of Human Germline Genome Editing
Jointly submitted by
The Ethics Committee of the Catholic Medical Association
The National Catholic Bioethics Center
September 27, 2019
1. Which diseases and conditions, if any, do you see as appropriate for human germline genome editing?
Diseases and disorders appropriate for human germline genome editing would be precisely those diseases amenable exclusively to the ethical application of the technology and should only be ordered to serious, life-threatening diseases with the recommendation to focus on point mutations or easily identifiable short sequence mutations that improve outcomes to a proportionate degree. By ‘ethical application of the technology’ is meant only those procedures used to pursue ‘research’ or develop ‘cures’ for a genetic defect that does not involve harm to, or destruction of, any human subjects, especially human embryos and fetuses, to ensure that members of this vulnerable segment of the human population are not terminated or otherwise instrumentalized. This means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject.
2. If there were to be an appropriate use case for human germline genome editing, what evidence would be needed to proceed to first in human use?
Any procedures used to pursue ‘research’ or develop ‘cures’ for a genetic defect must not involve harm to, or destruction of, any human subjects, especially human embryos and fetuses, to ensure that members of this vulnerable segment of the human population are not terminated or otherwise instrumentalized. This means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject. Prior to any human attempts, multiple generations of healthy offspring of animals and non-human primates carrying a similar genetic defect, would have to be tracked after the introduction of genome edits, with verification of the absence of ‘off target,’ mosaic-type mutations, and other complications or unanticipated side-effects.
3. What is the status of editing mechanisms for early stage human embryos (e.g., using different editing techniques, improving homology directed repair, etc.)? What are the factors that predict whether single nucleotide changes or other intended modifications in human embryos will be correct? To what extent will genome editing affect the viability of embryos?
NO ANSWER PROVIDED.
4. What is the status of the technology for validating that a correct edit (on target characterization) has been made and that unintended edits (e.g., off target effects, mosaicism, etc.) have not occurred in a range of cell and tissue types? If possible, please provide evidence drawn from work on induced pluripotent stem cells, embryonic stem cells, and/or early stage human embryos.
NO ANSWER PROVIDED.
5. What is the status of generating cell lines from human and non-human germline stem cells?
NO ANSWER PROVIDED.
6. How might animal models inform the editing in human embryos (inclusive of analysis of phenotypic correction)?
NO ANSWER PROVIDED.
7. To what extent do different genetic backgrounds affect success and phenotypic outcomes after genome editing?
NO ANSWER PROVIDED.
8. What is the success rate of full term pregnancies following pre-implantation genetic diagnosis? What affects this (e.g., age, number of oocytes harvested, technique used, etc.)?
NO ANSWER PROVIDED.
9. What are the appropriate mechanisms for obtaining informed consent, long-term monitoring of the future children, assessing potential effects in subsequent generations, and addressing untoward effects? Are there best practices from: a) assisted reproductive technologies; b) pre-implantation genetic diagnosis; c) gene transfer research for children; d) mitochondrial replacement therapy; and e) somatic genome editing?
If ethical considerations for the technology were duly satisfied and safeguarded, (i.e., that any procedures used to pursue ‘research’ or develop ‘cures’ for a genetic defect must not involve harm to, or destruction of, any human subjects, especially human embryos and fetuses, to ensure that members of this vulnerable segment of the human population are not terminated or otherwise instrumentalized; this means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject), and human genome editing were to be pursued, then a National and/or International Registry would need to be instituted that would oversee and regulate such activities in order to track current and foreseeable future generations of persons undergoing germline genome editing, to identify and catalogue untoward effects and future unanticipated outcomes. In terms of consent, standard requirements for patient consent would have to be followed. This means that proxy consent could be sought from parents when treatments for under-age children were being considered. Parents can never grant valid informed consent for research experimentation upon, or destructive utilization of, their embryonic children.
10. How should we think about the inter-generational medical (e.g., genetic changes to the genome) and ethical implications of human germline genome editing (e.g., potential harms and benefits)? How should the rights of future generations and the wider human population be taken into account?
Genome editing which bio-enhances otherwise healthy humans should be banned. Further discussion regarding the distinction between enhancement and therapeutic interventions will be required, but the principle that bio-enhancement constitutes an unethical use of genome editing should be recognized. Not doing so and allowing for bio-enhancements has the potential to generate two classes of human beings: natural and bio-enhanced, leading to potential unjust and conflictual societal stratification. Any procedures used to pursue ‘research’ or develop ‘cures’ for a genetic defect must not involve harm to, or destruction of, any human subjects, especially human embryos and fetuses, to ensure that members of this vulnerable segment of the human population are not terminated or otherwise instrumentalized. This means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject.
11. What international oversight structures would need to be in place to facilitate, in a responsible way, a path forward for germline genome editing?
If and only if, procedures are developed to pursue such research ethically (as defined by procedures that do not harm or destroy any human subjects, especially human embryos and fetuses, in order to ensure that members of this vulnerable segment of the human population are not terminated or otherwise instrumentalized; this means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject), then National and International Registries with ethical oversight and enforcement must be in place prior to conduct of such ethical germline genome editing procedures. There should be strict licensure and regulation of clinics and laboratories performing such activities.
Such Registries/oversight bodies should be comprised of scientists, governmental regulators, ethicists, theologians, religious representatives, and disease advocacy groups. Special care must be taken with respect to composition of these entities to avoid over-representation of researchers and commercial groups standing to profit from the promulgation of the technology. Moreover, voices that are likely to speak contrary to the will of researchers, universities, and commercial interests, especially voices from the Catholic Church, must not be excluded as tends to occur when scientists seek to forcibly gain control over the ethical discourse and assure favorable or pre-determined outcomes. All proceedings of such oversight bodies must be publicly available, and closed-door, back-room sessions and decision-making must be explicitly disallowed.
12. Are there any topics or issues that are not covered by the above questions that you think the Commission should attend to during its deliberations?
As a practical matter currently, germline genome editing of the gestating or born human employing present-day technologies should not be pursued. Such an affirmation is not an “in principle” objection as much as an objection based on a number of ethically problematic steps currently required for performing human germline modifications along with a number of other variables that could reasonably be expected to have relevance in terms of risks to the patient, risks to future generations, and other unanticipated outcomes or harmful “side effects.” These ethically problematic steps include the instrumentalization, harming, and/or destruction of human subjects, especially human embryos and fetuses, This means that direct embryonic creation through in vitro fertilization or extra-corporeal embryo creation must not be employed at any point in the process, and that single subjects, naturally conceived in the marital embrace and gestating, or already born, would need to be the subjects of such interventions, assuming the presence of valid therapeutic needs of the subject.