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514 Gyngell C, et al. J Med Ethics 2019;45:514–523. doi:10.1136/medethics-2018-105084

Moral reasons to edit the human genome: picking up
from the Nuffield report
Christopher Gyngell,1,2 Hilary Bowman-Smart,  2 Julian Savulescu2,3

Feature article

To cite: Gyngell C,
Bowman-Smart H,
Savulescu J. J Med Ethics
2019;45:514–523.

1Department of Paediatrics,
University of Melbourne,
Melbourne, Victoria, Australia
2Murdoch Children’s Research
Institute, Melbourne, Victoria,
Australia
3Faculty of Philosophy, Oxford
Uehiro Centre for Practical
Ethics, Oxford, UK

Correspondence to
Professor Julian Savulescu,
Faculty of Philosophy, The
Oxford Uehiro Centre for
Practical Ethics, Oxford OX1
1PT, UK;
julian. savulescu@ philosophy.
ox. ac. uk

Received 7 September 2018
Revised 2 December 2018
Accepted 11 December 2018
Published Online First
24 January 2019

► http:// dx. doi. org/ 10. 1136/
medethics- 2018- 105316

► http:// dx. doi. org/ 10. 1136/
medethics- 2019- 105390

► http:// dx. doi. org/ 10. 1136/
medethics- 2019- 105395

► http:// dx. doi. org/ 10. 1136/
medethics- 2019- 105713

© Author(s) (or their
employer(s)) 2019. Re-use
permitted under CC BY.
Published by BMJ.

AbsTrACT
In July 2018, the Nuffield Council of Bioethics released
its long-awaited report on heritable genome editing
(HGE). The Nuffield report was notable for finding that
HGE could be morally permissible, even in cases of
human enhancement. In this paper, we summarise the
findings of the Nuffield Council report, critically examine
the guiding principles they endorse and suggest ways
in which the guiding principles could be strengthened.
While we support the approach taken by the Nuffield
Council, we argue that detailed consideration of the
moral implications of genome editing yields much
stronger conclusions than they draw. Rather than being
merely ’morally permissible’, many instances of genome
editing will be moral imperatives.

InTroduCTIon
Genome editing technologies have developed
rapidly in the last few years, and point to a future
where we can precisely edit the human germline.
The most powerful gene editing technology is the
CRISPR (Clustered Regularly Interspaced Short
Palindromic Repeats)-Cas9 system. CRISPR-Cas9 is
found naturally in bacteria, where it functions as a
defence against viruses by cutting viral DNA into
small, non-functional fragments. In 2012, a team at
UC Berkeley showed that CRISPR-Cas9 could be
modified in the lab, so that it could target virtu-
ally any DNA sequence.1 This allows researchers
to cut effectively any part of the genome. Further-
more, once a DNA strand is broken, the cell’s own
repair mechanisms could be recruited to delete,
add or modify the sequence. In April 2015, it was
announced that CRISPR had been used to make
edits in human embryos for the fi

Computational and Structural Biotechnology Journal 18 (2020) 887–896

journal homepage: www.elsevier.com/locate/csbj

Review

Ethical issues related to research on genome editing in human embryos

https://doi.org/10.1016/j.csbj.2020.03.014
2001-0370/� 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

⇑ Corresponding author.
E-mail addresses: [email protected] (E. Niemiec), [email protected]

(H.C. Howard).

Emilia Niemiec ⇑, Heidi Carmen Howard
Centre for Research Ethics and Bioethics, Uppsala University, Box 564, 751 22 Uppsala, Sweden

a r t i c l e i n f o a b s t r a c t

Article history:
Received 15 November 2019
Received in revised form 13 March 2020
Accepted 14 March 2020
Available online 21 March 2020

Keywords:
Genome editing
CRISPR-Cas9
Oocyte donation
Egg donation
Whole genome sequencing
Research ethics

Although the potential advantages of clinical germline genome editing (GGE) over currently available
methods are limited, the implementation of GGE in the clinic has been proposed and discussed. Ethical
issues related to such an application have been extensively debated, meanwhile, seemingly less attention
has been paid to ethical implications of studies which would have to be conducted in order to evaluate
potential clinical uses of GGE.
In this article, we first provide an overview of the debate on potential clinical uses of GGE. Then, we

discuss questions and ethical issues related to the studies relevant to evaluation of potential clinical uses
of GGE. In particular, we describe the problems related to the acceptable safety threshold, current tech-
nical hurdles in human GGE, the destruction of human embryos used in the experiments, involvement of
egg donors, and genomic sequencing performed on the samples of the research participants.
The technical and ethical problems related to studies on GGE should be acknowledged and carefully

considered in the process of deciding to apply technology in such a way that will provide benefits and
minimize harms.

� 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and
Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.

org/licenses/by/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ARTICLE

Civil liability for damages related to germline
and embryo editing against the legal admissibility
of gene editing
Dorota Krekora-Zając 1✉

ABSTRACT The creators of CRISPR-Cas9 method have turned to the world community,

including lawyers, to undertake a public discussion on the implications that it can create. One

of the most important problems to be resolved in the future, will be the issue of establishing

very clear legal principles of compensatory liability for damages resulting from the editing of

genes in human embryos and reproductive cells. It is necessary to show possible legal

problems that may arise and—what is more—the fact that they will certainly appear in future

legislative work in the world. Questions must be asked to which world legal experts will seek

answers. And this is the goal of this paper was set—showing possible legal problems and

asking questions related to liability for damages resulting from the editing of genes in human

embryos and reproductive cells that will be answered in the future. The most important

research questions are therefore: what is the genetic nature of the genes edition—is it a

treatment whose aim is to treat infertility of parents or the future child? How to determine

the scope of responsibility in the situation when it comes to the “cure” of one mutation, but

there is a tendency to develop a disease in the future? What then is the scope of the doctor’s

duty to inform? How to qualify the editing of a gene that is not intended to cure the existing

disease, but to obtain a certain specific immunity? What legal obligations will weigh on

parents who decide to edit the genes of the embryo or in the preconception phase? Finally,

the question arises about the time limits of this gene-editing responsibility. If we make

genetic modification of hereditary nature, then will the children or grandchildren subjected to

gene editing be able to make claims? In this paper, the provisions of international European

law, common law and continental law on the example of Polish law have been analysed. The

key findings of this paper are to show that legal problems in gene editing are not limited to

answering the question whether it should be admissible or not. For this reason, the role of

legal discourse, and in particular of private law, should focus on the reinterpretation of

traditional compensation structures, so that they also protect the rights of people whose

genome has been modified.

The newest developments in genome editing will demand that we think again about how to balance hope and fear
(Caroll and Charo, 2015).

https://doi.org/10.1057/s41599-020-0399-2 OPEN

1 Department of Civil Law, Faculty of Law and Administration, Warsaw’s

cells

Review

CRISPR-Cas and Its Wide-Ranging Applications: From Human
Genome Editing to Environmental Implications, Technical
Limitations, Hazards and Bioethical Issues

Roberto Piergentili 1 , Alessandro Del Rio 2,*, Fabrizio Signore 3, Federica Umani Ronchi 2, Enrico Marinelli 2

and Simona Zaami 2

����������
�������

Citation: Piergentili, R.; Del Rio, A.;

Signore, F.; Umani Ronchi, F.;

Marinelli, E.; Zaami, S. CRISPR-Cas

and Its Wide-Ranging Applications:

From Human Genome Editing to

Environmental Implications,

Technical Limitations, Hazards and

Bioethical Issues. Cells 2021, 10, 969.

https://doi.org/10.3390/cells10050969

Academic Editor: Tetsushi Sakuma

Received: 31 March 2021

Accepted: 19 April 2021

Published: 21 April 2021

Publisher’s Note: MDPI stays neutral

with regard to jurisdictional claims in

published maps and institutional affil-

iations.

Copyright: © 2021 by the authors.

Licensee MDPI, Basel, Switzerland.

This article is an open access article

distributed under the terms and

conditions of the Creative Commons

Attribution (CC BY) license (https://

creativecommons.org/licenses/by/

4.0/).

1 Institute of Molecular Biology and Pathology, Italian National Research Council (CNR-IBPM),
00185 Rome, Italy; [email protected]

2 Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Sapienza University of Rome,
00161 Rome, Italy; [email protected] (F.U.R.); enric[email protected] (E.M.);
[email protected] (S.Z.)

3 Obstetrics and Gynecology Department, USL Roma2, Sant’Eugenio Hospital, 00144 Rome, Italy;
[email protected]

* Correspondence: [email protected] or [email protected]

Abstract: The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organ-
isms, inc

REVIEW
published: 07 August 2020

doi: 10.3389/fonc.2020.01387

Frontiers in Oncology | www.frontiersin.org 1 August 2020 | Volume 10 | Article 1387

Edited by:

Israel Gomy,

Dana–Farber Cancer Institute,

United States

Reviewed by:

Nan Wu,

Peking Union Medical College

Hospital (CAMS), China

Tanja Kunej,

University of Ljubljana, Slovenia

Martin Roffe,

A.C. Camargo Cancer Center, Brazil

*Correspondence:

Charles M. Rudin

[email protected]

Triparna Sen

[email protected]

†Lead Contact

Specialty section:

This article was submitted to

Cancer Genetics,

a section of the journal

Frontiers in Oncology

Received: 09 March 2020

Accepted: 30 June 2020

Published: 07 August 2020

Citation:

Uddin F, Rudin CM and Sen T (2020)

CRISPR Gene Therapy: Applications,

Limitations, and Implications for the

Future. Front. Oncol. 10:1387.

doi: 10.3389/fonc.2020.01387

CRISPR Gene Therapy: Applications,
Limitations, and Implications for the
Future
Fathema Uddin1, Charles M. Rudin1,2* and Triparna Sen1,2*†

1 Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY,

United States, 2 Weill Cornell Medicine, Cornell University, New York, NY, United States

A series of recent discoveries harnessing the adaptive immune system of prokaryotes

to perform targeted genome editing is having a transformative influence across the

biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic

Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications

of genetic research in thousands of laboratories across the globe and is redefining our

approach to gene therapy. Traditional gene therapy has raised some concerns, as its

reliance on viral vector delivery of therapeutic transgenes can cause both insertional

oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle,

CRISPR technology provides a relatively simple and efficient alternative for site-specific

gene editing, obliviating some concerns raised by traditional gene therapy. Although it

has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be

addressed for safe and efficient clinical translation. This review focuses on the evolution

of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review

the emerging dat

Leading Edge

Review

Heritable human genome editing:
Research progress, ethical considerations,
and hurdles to clinical practice
Jenna Turocy,1 Eli Y. Adashi,2 and Dieter Egli1,3,4,*
1Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA
2Professor of Medical Science, Brown University, Providence, RI, USA
3Department of Pediatrics and Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA
4Columbia University Stem Cell Initiative, New York, NY 10032, USA
*Correspondence: [email protected]

https://doi.org/10.1016/j.cell.2021.02.036

ll

SUMMARY

Our genome at conception determines much of our health as an adult. Most human diseases have a heritable
component and thus may be preventable through heritable genome editing. Preventing disease from the
beginning of life before irreversible damage has occurred is an admirable goal, but the path to fruition remains
unclear. Here, we review the significant scientific contributions to the field of human heritable genome edit-
ing, the unique ethical challenges that cannot be overlooked, and the hurdles that must be overcome prior to
translating these technologies into clinical practice.

INTRODUCTION

The introduction of genome editing using clustered regularly

interspaced short palindromic repeats (CRISPR)-based tech-

nologies generated tremendous enthusiasm as well as con-

troversy within the medical and public communities. Herita-

ble Human Genome Editing (HHGE) has the potential to

treat or even eradicate genetic diseases. By addressing ge-

netic disease before the defect is amplified through cell pro-

liferation during development, HHGE may prove to be more

effective than any other treatment being developed today,

including somatic gene or drug therapy (Figure 1). Somatic

gene therapies are limited in their ability to reverse damage

that has already occurred and to reach the billions of cells

needed to adequately treat the disease. The brief in vitro

culture of a human embryo as routinely practiced in IVF

clinics provides a readily accessible window for potential

prevention of numerous conditions that later in life are diffi-

cult to manage, let alone cure. This hope provides the ratio-

nale for research, but not yet for therapy, as criteria of effi-

cacy and safety have yet to be met. HHGE also raises

difficult ethical and regulatory questions. Manipulations of

the early embryo are highly consequential, both with regard

to potential benefits but also with regard to risks. Other re-

views have also discussed heritable genome editing, empha-

sizing

Commentary

Gene editing and the health of future generations

Christopher Gyngell
Oxford Uehiro Centre for Practical Ethics, Oxford University, Oxford OX1 3PA, UK

Corresponding author: Christopher Gyngell. Email: [email protected]

The CRISPR-cas9 gene-editing system (CRISPR) is a
revolutionary technology that promises unparalleled
abilities. It is the first technology that allows for the
precise, efficient modification of DNA sequences. Less
than five years since it was first developed, it has been
used to alter a diverse range of organisms, including
plants, livestock, insects and primates. There is little
doubt that it will soon be technically possible to use
the CRISPR system to rewrite the human genome. It is
crucial that we consider the impact such technologies
will have on future generations. The ability to alter our
biological makeup will create immense opportunities
but also pose novel threats. It is crucial that we make
sensible decisions about the development and use of
gene-editing technologies.

In this commentary, I discuss the effect that germ-
line gene editing will have on the health of future gen-
erations (Note: By ‘germline’ gene editing, I mean the
editing of DNA in cells which could potentially be her-
itable, e.g. germ cells or embryonic cells.). I argue that
provided germline gene editing is well regulated, it
could greatly improve the health of our descendants.
The use of germline gene editing in research will greatly
increase our knowledge of development and could lead
to novel treatments for disease. Germline gene editing
also has enormous potential as a clinical tool. It could
soon be used to prevent simple genetic diseases, and
eventually to reduce the incidents of polygenic dis-
eases. While the use of germline gene editing to prevent
disease raises contentious philosophical issues, concep-
tual uncertainty should not prevent the development of
germline gene editing as a research tool and a treatment
for fatal genetic conditions.

The research applications of germline gene
editing

The most significant question currently facing coun-
ties in regards to germline gene editing is whether to
use germline gene editing for research purposes. In
many countries around the world, such as Canada,
Australia and most of Europe, any form of research

using germline gene editing is banned. Many of these
bans were legislated in eras of far cruder genetic
engineering technologies. Gene-editing techniques
like CRISPR-cas9 are much more precise and effi-
cient than previous methods, and are the first tech-
nologies with serious potential to be used to modify
the human germline.

The research case in favour of pursuing germline
gene editing is very strong.

1
Editing

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