Ethics and Gene Editing in Human

Embryos: ISSCR Policy

Jonathan Kimmelman
STREAM (Studies of Translation, Ethics and Medicine)
McGill University

Guidelines 2.0

lab
studies

therapeutic
trials
assisted
reproduction

respecting cultural differences

(setting a baseline)
respecting political differences
(e.g. mechanism)

Principles

biomedical research is a collective endeavor. It

depends on the contributions of many kinds of individuals,
including basic scientists, clinicians, [and] patients...
Ethics principles and guidelines help secure the basis for
this collective endeavor

Principles
Integrity of the Research Enterprise
Respect for Subjects
Social Justice
Transparency
Primacy of Patient Welfare

research should be overseen by qualified

investigators and coordinated in a manner that is
sustainable and ensures that the information obtained
will be trustworthy, reliable, accessible, and
responsive to scientific uncertainties and priority
health needs. Doing so entails the need for
independent peer review, transparency, and
continued monitoring at each stage of research

Parties to the testing and application of

stem cell-based interventions should
promote timely exchange of accurate
scientific information to other interested
parties

Physicians and physician-researchers owe their

primary duty to the patient and/or research
subject. They must never unduly place
vulnerable patients at risk. Clinical testing
should never allow promise for future patients to
override the welfare of current research subjects.
Application of stem cell-based interventions
outside of formal research settings should be
evidence-based, subject to independent expert
review, and serve patients best interests

gene editing

?
hEmbryo

1. Process
2. Substance

EMRO

review
approval
ongoing monitoring

1. Process
2. Substance

research involving the genetic manipulation

of human embryos or gametes used to make
embryos in vitro

criteria

scientific merit
expertise of investigators
ethical justification

In vitro culture of any postfertilization human embryo or organized

cellular structure that might manifest
human organismal potential, regardless
of derivation method, beyond 14 days or
formation of the primitive streak,
whichever occurs first. This prohibition
extends to experiments whereby human
embryos or organized cellular structures
that might manifest human organismal
potential are gestated in any non-human
animal uterus.

ISSCR

nDNA
modification

hEmbryo

in vitro

>14d;
primitive
streak

nDNA
modification

hEmbryo

ISSCR

in vivo
nonhuman

>14d;
primitive
streak

Research in which human

embryos that have undergone
modification of their nuclear
genome are implanted into or
gestated in a human or nonhuman uterus . Genomemodified human embryos
include human embryos with
edits to their nuclear DNA and/or
embryos generated from a
human gamete that has had its
nuclear DNA modified.

nDNA
modification

hEmbryo

ISSCR

implantation

gamete

ISSCR

nDNA
modification

hEmbryo

implantation

Emerging Categories of Embryos Research

That Merits Close Review
Recommendation 2.1.4

Recommendation 2.1.4: The ISSCR supports

laboratory-based research that entails
modifying the nuclear genomes of gametes,
zygotes and/or pre-implantation human
embryos, performed under a rigorous EMRO
process.

Recommendation 2.1.4:
Such research will enhance fundamental
knowledge and is essential to inform any
thoughtful deliberations about the potential
safety and use of nuclear genome editing in
strategies aimed at preventing the
transmission of genetic disorders

Recommendation 2.1.4:
until further clarity emerges on both
scientific and ethical fronts, the ISSCR holds
that any attempt to modify the nuclear
genome of human embryos for the purpose
of human reproduction is premature and
should be prohibited at this time.

a) safety and long term risks

b) public and international dialogue

on the capabilities and limitations
of their application to the human
germ line

In contrast, mitochondrial replacement

therapy employs distinct methods and does
not entail direct modification to the nuclear
genomeThe Guidelines documented
herein and below provide plausible
mechanisms of review, approval, and
oversight

Principles
Integrity of the Research Enterprise
Respect for Subjects
Social Justice
Transparency
Primacy of Patient Welfare

Parties to the testing and application of stem

cell science should promote timely exchange
of accurate scientific information
Investigators should communicate with various
publics... Research teams should promote
open and prompt sharing of ideas, data and
materials.

Recommendation 3.2.4.1: Sponsors,

researchers, and clinical investigators
should publish preclinical studies in full,
and in ways that enable an independent
observer to interpret the strength of the
evidence supporting the conclusions.

3 unresolved points :

1) biosafety

2) non-edited (e.g. lenti)

3) noninheritable (in utero, episomal)

National Academies of Science

Engineering and Medicine
Human Genome Initiative

It would be irresponsible to proceed with any clinical use of germline editing unless and until
(i) the relevant safety and efficacy issues have been resolved, based on appropriate
understanding and balancing of risks, potential benefits, and alternatives, and
(ii) there is broad societal consensus about the appropriateness of the proposed application.
Moreover, any clinical use should proceed only under appropriate regulatory oversight.
At present, these criteria have not been met for any proposed clinical use: the safety issues
have not yet been adequately explored; the cases of most compelling benefit are limited; and
many nations have legislative or regulatory bans on germline modification.
However, as scientific knowledge advances and societal views evolve, the clinical use of
germline editing should be revisited on a regular basis.

Statement of Task: The study will examine the scientific underpinnings as well as the clinical, ethical, legal, and social
implications of the use of human genome editing technologies in biomedical research and medicine. .
What is the current state of the science of human gene editing, as well as possible future directions
What are the potential clinical applications
What is known about the efficacy and risks of gene editing in humans, and what research might increase the specificity and
efficacy of human gene editing while reducing risks?
Can or should explicit scientific standards be established for quantifying off-target genome alterations
Do current ethical and legal standards for human subjects research adequately address human gene editing What are the
ethical, legal, and social implications of the use of current and projected gene-editing technologies in humans?
What principles or frameworks might provide appropriate oversight for somatic and germline editing in humans? Are there
examples of how these issues are being addressed in the international context?
What are the prospects for harmonizing policies? What can be learned from the approaches being applied in different
jurisdictions?
The committee will address these questions and prepare a report that contains its findings and recommendations. The report
will provide a framework based on fundamental, underlying principles that may be adapted and adopted by any nation that is
considering the development of guidelines. The report will also include a focus on advice for the United States.

Public Meetings
Meeting #1
The committee held a brief open session in which they discussed the charge with the study sponsors.
December 3, 2015 (4:00 pm eastern) Washington, DC
Meeting #2: The committee will hear input from select stakeholder groups.
When: February 11, 2016 (8:00 am eastern)
Where: Washington, DC, Keck Center of the National Academies
Meeting #3: The committee will hear input from the international community. This will be the final public meeting of the
consensus committee.
When:
April 29-30, 2016
Where:
Europe (city TBD)

Committee
Members

For more information:

http://nationalacademies.org/gene-editing/consensusstudy/index.htm

Current and possible research

applica2ons using human germline
genome edi2ng
Amander Clark PhD
Professor and Vice Chair
Molecular Cell and Developmental Biology
University of California, Los Angeles
Eli and Edythe Broad Center for Regenera2ve Medicine and Stem
Cell Research

Informed Consent for human embryo

research

Donated embryos will not be used to create a baby

Growing interest in human embryo

dona2on for research purposes
Donors consented per year

100

50

0
20
07
20
08
20
09
20
10
20
11
20
12
20
13
20
14
20
15

Number of donors

150

Year embryos were received

Strong support from donors for research

into human embryo development
32%

38%

Human embryo development

Stem cell research
Human embryo and stem cell research

30%
Research preferences at 2me of consent
Kalista et al., Cell Stem Cell 2013

Basic Research ques2ons

Improving IVF
outcomes

Improving
Stem cells and
Regenera2ve medicine

Fidelity of CRISPR
in human embryos