May 17, 2019 Breakthroughs in genetics have often raised complex ethical and legal questions, which loom ever larger as genetic testing is becoming more commonplace, affordable, and comprehensive and genetic editing becomes poised to be a consumer technology. As genetic technologies become more accessible to individuals, the ethical and legal questions around the consumer use of these technologies become more pressing. As these questions become more pressing, now is the time to re-consider what ethical and regulatory safeguards should be implemented and discuss the many questions raised by advancements in consumer genetics. Presentation: Scott Schweikart, Senior Research Associate, Council on Ethical and Judicial Affairs, American Medical Association and Legal Editor, AMA Journal of Ethics - Human Gene Editing: An Ethical Analysis and Arguments for Regulatory Guidance at Both the National and Global Levels Learn more: https://petrieflom.law.harvard.edu/events/details/2019-petrie-flom-center-annual-conference

1. Human Genome Editing:
An Ethical Analysis and Arguments for
Regulatory Guidance at Both the National
and Global Levels
Scott J. Schweikart, JD, MBE

2. Introduction: Genome Editing is
Raising Profound Ethical Concerns
Image: VOA/Iris Tong
Image: TotallyMJ/Shutterstock

3. Genome Editing Technologies
Meganucleases, ZFNs and TALENs
Predominantly used methods of gene
editing technology before the advent of
CRISPR.
Disadvantages is that they are more
expensive and technically challenging.
Require protein engineering to target
specific DNA sequences, hence the expense
and technical challenges.
CRISPR-Cas9
Advantage of being less expensive and
more precise other nucleases
Use of guide RNA strand to guides Cas9
nuclease enzyme to desired part of genome
Edits can be then performed by Homology
Directed Repair or Non-Homologous End
Joining
Image: molekuul_be/Shutterstock

4. Ethical Considerations:
Somatic vs. Germline Genome Editing
Somatic
 Targets some of an individual’s
cells, but NOT the germline; any
edits will not be transmitted to the
next generation.
 Potential therapeutic uses include
cancer, treatments for sickle cell.
Germline
 Also known as “heritable
genome editing”; involves cells of
the germline, i.e., gametes, zygotes,
and embryos.
 Edits may pass sexually and
thus generationally; potential to
shape human evolution.

5. Principles of
Biomedical
Ethics
• Autonomy
• Non-maleficence
• Beneficence
• Justice
Image: Beauchamp and Childress/Oxford University Press

6. Autonomy
Individual liberty, privacy, choice, and freedom of will.
 Relevant for both somatic and germline editing: With both
somatic and germline editing, at issue is an individual’s desire to modify
their own body, or more specifically, their genome.
 Autonomy of future generations: With germline editing, how can
the consent of future generations be obtained? Can the autonomy of
future generations be violated if they have not yet come into existence?

7. Non-maleficence and Beneficence
“Do no harm” (non-maleficence) and “act for the benefit of
others” (beneficence).
 Weighing of the potential harms and benefits
 Therapeutic treatment or enhancement
 Safety concerns: off-target effects and significant unknowns of
genome editing
 Genetic Essentialism: view of how essential or determinative genetics
are in the human identity; nature vs. nurture debate

8. Social Justice
 Fair and Equitable: Justice is derived from what is fair and equitable.
 Widen Gaps: Potential to further widen gaps between advantaged and
disadvantaged members of society.
 Access: Wealthy may have greater access to genome editing, including
“enhancements” of desirable social and physical traits, furthering social
divide.
Human rights: Potential exists for new forms discrimination based on
genetic status.

9. Example of Different Weighing of
Values: Treatment vs. Enhancement
 National Academies recommend that
regulatory agencies not allow genome
editing for enhancement purposes.
 Nuffield Council recommendation is open to
allowing enhancement editing, provided
that concerns about welfare of the individual
and society are considered and met.
Different weighing of “genetic essentialism” (subject to different priorities and values)
may account for difference in regulatory recommendation.
[Credit: Eli Adashi and Glenn Cohen note this observation. Adashi EY, Cohen IG, The Ethics of Heritable Genome Editing: New Considerations in a
Controversial Area, 320(24) JAMA 2531 (2018).]

10. National Regulations
Scope: Scope of national regulations should encompass both somatic and germline
editing.
 Administrative Safety and Efficacy Regulations: FDA evaluating safety and
efficacy of research and therapies.
 Research Funding: NIH will not fund research involving germline genome
modification. Dickey-Wicker Amendment prohibits any funding to create a human
embryo or modify a human embryo, including heritable modification.
 Tort Law: How tort law develops has potential to act as a regulatory driver.
 Patent Law: Moral or beneficial utility doctrine and license restrictions have potential
to influence ethical usage of new technologies.
Image: dikobraziy/Shutterstock

11. Global Regulations
Scope: Germline editing must be encompassed by global regulations, as the
consequences are international and global in nature.
 International Collaboratives: International treaties or collaboratives with binding
force between nation states are one, although perhaps unlikely, route.
 International Decree: Another alternative is to create an international decree, that
would give guidance to nations about how to approach regulation of germline editing.
Image: IndianSummer/Shutterstock

12. German Ethics Council Recommendation
on Germline Editing
 Council does not consider germline editing to be “inviolable”, meaning
that editing is not impermissible absolutely; in certain conditions it can be
ethically performed.
 Currently there should be a moratorium on germline editing because of
the “incalculable risks” associated.
 Governments work together to create a binding international agreement.
 https://www.ethikrat.org/en/press-releases/2019/ethics-council-germline-interventions-currently-too-risky-but-not-
ethically-out-of-the-question/
 https://www.ethikrat.org/fileadmin/Publikationen/Stellungnahmen/englisch/opinion-intervening-in-the-human-
germline-summary.pdf

13. Concluding
Remarks
• Heritable genome
editing requires special
regulatory attention at a
global scale
• Prudence is necessary
in the face of unknown
risks coupled with
potentially large
consequences
• German Council
recommendation may
provide a balanced and
prudent approach
Image: Lonely/Shutterstock

14. Thank you!
Scott J. Schweikart, JD, MBE
American Medical Association
Chicago, Illinois
scott.schweikart@ama-assn.org
@ScottSchweikart