TABLE 2.

Example of questions for conducting careful scientific research, ethical, legal, and social issues (ELSI) research, and meaningful stakeholder engagement, education, and dialogue (SEED) in context of gene editing.

Aspects	Example of questions
Building a scientific evidence base for gene editing
Carry out ongoing responsible scientific research to create a solid foundation of facts, especially with regard to risks and benefits	• Is the current standards and practices of sharing academic and commercial research results, in particular with regard to risks and benefits, adequate for the current and future gene editing field? • Should there be a common framework developed for tracking (systematically) all forms of basic and (pre) clinical research? • If so, which kind of work does it take to adhere to this? All research, or just work done in human cells? • Who should/will be taking responsibility for tracking or reporting this? where does the funds come from to coordinate and support those efforts? • How would a long-term medical monitoring of human patients be coordinated informatively? • Will the patients be expected to agree to lifelong follow up after treatment? How should this be achieved while preserving individual autonomy? • For each of the above questions, who should decide the answers to these questions? Based on what criteria?
Ethical, legal, and social issues research (ELSI) of gene editing
Somatic cell gene Therapy	• Do we require any changes to the existing legal structure to tackle somatic gene therapy? If so, who would form the legal structure any further? • Are the principles and procedures present in clinical trials sufficient? • How can somatic gene therapy trials be performed and assessed? • Do we require specific patient protection or status in these trials? • What are the protocols to be established for patients undergoing these treatments (i.e.: consent, genetic counseling, follow-up monitoring)? • To what degree will commercial companies be willing, or be allowed to offer, potentially upon consumer request, treatments based on therapies, where so much vagueness regarding likely harm? • Which healthcare practitioners should engage in the implementation of somatic gene therapy and the care of patients receiving these treatments? • How are we going to ensure equal access to the technology? • How do we ensure the need drives the usage and not the technical imperative? • Who will determine on roles and obligations in this novel context? • What criteria will be used to select the eligible diseases/populations to be treated? • How do we ensure that research funding is distributed proportionally to the amount of gene editing work being carried out?
Germline gene therapy	• Will gene editing of human germ line cells, gametes and embryos be permitted in basic science, for better knowledge of human biology (i.e.: human development) and without planning to be used to establish modified human life? • Should gene editing of germ line cells, gametes, or embryos or any other cell resulting in heritable modification be allowed in a clinical setting for humans? • Would any principles or reasoning justify the use of germline gene editing in humans in a clinical context, given the existing ban on such techniques in many jurisdictions? • Why should we consider using germline gene editing in the clinic when there are alternative ways in which couples can have healthy (biologically related) children? Who will decide? Based on what criteria? • Before considering germline gene editing, would we first understand the risks and benefits of somatic gene editing? • What are the functions and duties of the various parties involved in those decisions? • How do commercial incentives and the technological imperative play a role in these decisions? • If we entertain gene editing for reproductive use, what criteria would be considered safe according to various stakeholders (scientist, ethicists, clinicians, policy makers, patients, lay public)? Who will set this safety threshold and based on what risk/benefit calculations? • If germline gene editing was allowed, how would the fact that for the first time, a human would be directly editing the nuclear DNA of another human in an inherited manner cause some form of segregation of types of humans? • If ever permitted, should germline gene editing be limited only for specific medical purposes with a particular high probability of developing a disease, and if so, does it matter if the risk is not 100%, but much lesser? • How do we define/demarcate medical reasons from enhancement? And, as was posed above for the use in somatic cells, for what medical conditions will gene editing be deemed suitable for use? What will the criteria be and who will decide?
Stakeholder, engagement, education and dialogue (SEED) for gene editing
Planting SEEDs for gene editing	• What are the roles and obligations do various stakeholders have in developing and sustaining engagement, education and dialogue? • What will, and what should be the role of scientists and other academics in this type of popular media communications, and engagement activities? • As public engagement can have multiple goals, before each activity, we must consider: What are our objectives? And, what strategy of engagement will best meet these objectives? • How will the mass of voices we want to include in public engagement be weighed against each other? How are we to make sure every voice is heard? • What position will feedback and preferences of various stakeholders play in the discussion and decision-making process? How will those opinions be balanced and treated in policy making? • How can we ensure that public education is not limited to a token work package in science grants and/or to campaigns that try to persuade for or against gene editing? • How can we ensure that such public education and engagement is available to everyone, including in countries that currently may not have the resources to take on such SEED activities?

Adapted and modified from Howard et al. (2018).