Last week, I discussed efforts by a US/UK commission formed to recommend a framework for regulating and monitoring heritable human gene editing. This commission has called for “expert evidence” to assist them in the task “to develop a framework for considering technical, scientific, medical, regulatory, and ethical requirements for human germline genome editing, should society conclude such applications are acceptable.” The deadline is September 27, 2019 to make recommendations. The website to do so appears open to the public.
Now, I suppose the commission will ultimately decide who qualifies as an “expert,” and several of the questions are decidedly technical. But I submit that many who read this blog qualify as experts in bioethics or in some aspect of biomedicine, and will be able to offer considered responses to at least some of the questions. So I encourage readers of this blog to access the link and weigh in.
I have yet to complete my effort. I started last week, then pulled back in the middle. Responses to each question appear to be submitted in real time, and the possibility to save work (there are ‘”back” and “next” buttons) for future editing seemed unclear. And these questions merit careful responses. So I decided to wait for another day—before the September 27 deadline!
If you would like to mull over possible responses in advance of trying to offer them online, I have copied them here, for advance thinking before submitting at the online portal, or to inform reflection and discussion otherwise:
- Which diseases and conditions, if any, do you see as appropriate for human germline genome editing?
- 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?
- 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?
- 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.
- What is the status of generating cell lines from human and non-human germline stem cells?
- How might animal models inform the editing in human embryos (inclusive of analysis of phenotypic correction)?
- To what extent do different genetic backgrounds affect success and phenotypic outcomes after genome editing?
- 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.)?
- 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?
- 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?
- What international oversight structures would need to be in place to facilitate, in a responsible way, a path forward for germline genome editing?
- 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?
This last question, of course, is the most pregnant of all. The list of questions is so technical, so question-begging about whether heritable gene editing should be done at all, that the commission should receive carefully-considered reflections on the meaning of the potential enterprise, how the future practice of heritable genome editing should not be a foregone conclusion, and how and why the right answer to “when should we edit human genes heritably” might well be “never.”
By all means, reader of this blog, go online and offer what you reasonably can to this important discussion!