The Promise and Peril of CRISPR

Visit the link below to download the full version of this book:

https://medipdf.com/product/the-promise-and-peril-of-crispr/

Click Download Now

 For Caleb

Baer_CRISPR_int_4pgs.indd 5 05/03/24 1:22 AM

 This page intentionally left blank

349-99188_Rothfels_ch01_3P.indd 6
 Contents

Introduction: Code Dread? 1

Neal Baer

Part One: Overview—­The Era of CRISPR

1 CRISPR: Challenges Posed by a Dual-­Use Technology 25

Rachel M. West and Gigi Kwik Gronvall

Part Two: Ethical Questions Raised by CRISPR Technology

2 Untangling CRISPR’s Twisted Tales 45

Marcy Darnovsky and Katie Hasson

3 Heritable Genome Editing and International ­Human Rights 71

Kevin Doxzen and Jodi Halpern

4 Demo­cratizing CRISPR: Opening the Door or Pandora’s Box? 83

Ellen D. Jorgensen

5 Welcome to the CRISPR Zoo 92

Marcus Schultz-­Bergin

Part Three: Personal Perspectives

6 Who Goes First? 103

Carol Padden and Jacqueline Humphries

7 Billie Idol 115

Ethan Weiss

8 Curing Cystic Fibrosis? 124

Sandra Sufian

Part Four: Diverse Voices

9 CRISPR and Gene Editing: Why Indigenous ­Peoples

and Why Now? 133
Krystal Tsosie

Baer_CRISPR_int_4pgs.indd 7 05/03/24 1:22 AM

 viii Contents

10 Do Trans/Humanists Dream of Electric Tits?

CRISPR and Transgender Bioethics 139
Florence Ashley

Part Five: The Dilemma of Controlling the ­Future

11 Velvet Eugenics: In the Best Interests of Our ­

Future ­Children? 153
Rosemarie Garland-­Thomson

12 A Therapeutic Fallacy 172

Peter F. R. Mills

13 Genome Editing, in Time 185

Robert Sparrow

Part Six: Oversight and Monitoring

14 Regulating CRISPR: A Quest to Foster Safe, Ethical,

and Equitable Innovation 195
Andrew C. Heinrich

15 Should We Fear Heritable Genome Editing? 207

R. Alta Charo

16 Advancing Progressively Backwards: Guiding and Governing

Heritable Genome Editing 219
J. Benjamin Hurlbut

List of Contributors 245

Index 249

Baer_CRISPR_int_4pgs.indd 8 05/03/24 1:22 AM

 The Promise and Peril of CRISPR

Baer_CRISPR_int_4pgs.indd 9 05/03/24 1:22 AM

 This page intentionally left blank

349-99188_Rothfels_ch01_3P.indd 6
 Introduction

Code Dread?

Neal Baer

CRISPR keeps me up at night. I marvel at its potential to cure insidi-

ous ge­ne­tic diseases and scourges like malaria. I shudder at the ways it might
be misused to create biological weapons. What frightens me most, though,
is what I cannot predict: How w ­ ill we use CRISPR? Who w­ ill have the author-
ity to monitor its use? How ­will it change evolution? How ­will it redefine
the very nature of our existence?
CRISPR (clustered regularly interspaced short palindromic repeats) is an
ingenious cut-­and-­paste system that homes in on a par­tic­u­lar DNA gene se-
quence and snips it out using Cas9 enzymes. That sequence is then replaced
with a new one that rewrites or repairs it. Two dif­fer­ent cells—­somatic, from
the body, and germline, from gametes—­can be manipulated using CRISPR.
Only germline genome cells can be inherited by ­future offspring.
As I write this introduction in early 2024, breakthroughs are rapidly occur-
ring in CRISPR design and application, including research using CRISPR to
target RNA with Cas13 enzymes (known as CrRNA). Though we do not exam-
ine CrRNA in this volume, focusing instead on heritable genome editing
(HGE), this new variety of CRISPR could be used to “control the expression
of ­human genes in dif­fer­ent ways—­such as flicking a light switch to shut
them off completely or by using a dimmer knob to partially turn down their
activity” (New York University 2023, 2). A gene expression “modulator” could
be used to treat diseases like Charcot-Marie-Tooth, where an overabundance
of a protein is produced that c­ auses peripheral muscular paralysis, or in treat-
ing RNA viral infections.
Using CRISPR to treat ­human disease began in 2019, when scientists in
the United States used somatic editing to treat a patient with sickle cell dis-
ease. In ­Europe, scientists treated one with beta thalassemia. Both patients,

Baer_CRISPR_int_4pgs.indd 1 05/03/24 1:22 AM

 2 The Promise and Peril of CRISPR

suffering from ge­ne­tic mutations of their hemoglobin genes, underwent

bone marrow ablation. Then CRISPR was used to modify their blood-­
producing stem cells to make healthy fetal hemoglobin. The CRISPR cells
­were engrafted in each patient without the usual worry of donor rejection.
Both patients are reported to be d ­ oing well, making healthy fetal hemo-
globin. ­T hese CRISPR-­based treatments have kept them from needing
transfusions or hospitalization for severe anemia, vaso-­occlusive crises,
and strokes. Using CRISPR to treat ­these ge­ne­tic mutations that cause inor-
dinate suffering and a shortened life span is nothing short of miraculous,
though who ­will pay for this expensive treatment ­will come to the forefront
now that the FDA has approved a CRISPR treatment for sickle cell disease.
Why worry, then, about using CRISPR if it can be made safe in the clini-
cal setting? Repairing the somatic ge­ne­tic mutations in an individual means
that scientists can do the same to the germline genome, and this could change
­human evolution by making an edit in an embryo that ­will be inherited by
descendants. “That raises the possibility, more realistically than ever before,”
notes Michael Specter (2015), a well-­known science journalist, “that scientists
­will be able to rewrite the fundamental code of life, with consequences for
­future generations that we may never be able to anticipate” (54).
The impact of CRISPR goes beyond the ­human species. Any gene can po-
tentially be edited, w ­ hether in a person, animal, or plant—if it has a ge-
nome. Imagine editing crops to be drought tolerant or animals, like pigs, to
make organs that can be transplanted into h ­ umans (known as xenotransplan-
tation). ­These are not ideas in the realm of science fiction; CRISPR is used
­today on plants and animals to accomplish t­ hese feats and much more. Re-
cently, researchers edited genes in chicken cells by using CRISPR to create
“chickens that can resist real-­life doses of avian flu viruses.” However, “the
edited birds still became infected when exposed to larger amounts of the flu
virus. And the strategy raises a safety concern: chickens edited this way could,
in theory, drive the evolution of flu variants better at infecting ­people” (Co-
hen 2023, para. 1, 2).
Even more astounding is the potential to eliminate malaria with a
CRISPR-­based gene-­drive system that preferentially propagates a ge­ne­tic
trait through an organism and its offspring. Gene drives could be used to
make a female mosquito infertile, causing it to be incapable of laying eggs.
Instead of a 50% chance that the disruptive gene is inherited, a CRISPR gene
copies itself, making the inheritance 100%, leading to mosquitoes that could
extinguish their own species. The debate now focuses on ­whether to release

Baer_CRISPR_int_4pgs.indd 2 05/03/24 1:22 AM

 Introduction 3

t­ hese gene drives into malaria-­ridden communities and ­whether scientists

can ever truly predict the unintended ecological outcome of making a species
extinct.
Can we ever be certain of the environmental impact of such an undertak-
ing, even if it means preventing a thousand c­ hildren from ­dying of malaria
each day? Can we prevent the malevolent use of CRISPR to conjure up bac-
teria or viruses that can wipe out millions or destroy food crops the world
depends on? “If you can edit a creature to solve a prob­lem,” declares gene-­
drive discoverer Kevin Esvelt (2019), “you can edit a creature to create a
prob­lem” (5).
CRISPR has vaulted us into a binary world of hope and potential devas-
tation. It can provide cures that w ­ ill alleviate suffering along with terrifying
bioweapons that could destroy us. It can lead to somatic gene editing treat-
ments for diseases that assail humankind and germline gene-editing en-
hancements that could give the wealthy or empowered an even greater
societal edge. ­Political theorist Michael Sandel (2004) warns that this could
lead to two subspecies: “the enhanced and the merely natu­ral” (para. 13).
This dual-­use research of concern “could be directly misapplied by ­others to
pose a threat to public health and safety, agricultural crops and other plants,
animals, the environment, or materiel,” or national security (National Re-
search Council 2004, 17).
CRISPR is not the first exterminating peril the world has faced. Scientists
and inventors have given us nuclear weapons and fossil-­fuel engines that
have posed dire threats of nuclear winter and global warming. Since the
atomic bomb was dropped on Hiroshima and Nagasaki, nation-­states have
operated ­under the paradigm of mutually assured destruction: if you bomb
us with a nuclear weapon, we ­will retaliate. The threat of mutual annihila-
tion has averted nuclear Armageddon. With CRISPR, this old paradigm
has evaporated.
­Today, a rogue scientist with access to a DNA synthesizer, DNA sequences—­
which can be easily purchased—­and some basic scientific expertise can build
ge­ne­tic weapons of mass destruction. Scientists have already made horse­
pox, polio, and virulent avian flu (Yong 2018). CRISPR has also been used
to edit embryos, which w ­ ere not brought to term. Then, in 2018, twin girls
­were born with a CRISPR-­engineered germline mutation.
Dr. He Jiankui, a Chinese ge­ne­ticist, used CRISPR to manipulate the
germline of embryos that became the twins, claiming to have made them re-
sistant to HIV. An uproar ensued against He among scientists, journalists,

Baer_CRISPR_int_4pgs.indd 3 05/03/24 1:22 AM

 4 The Promise and Peril of CRISPR

and bioethicists. A few, however, like the Harvard ge­ne­ticist George Church,
supported him, claiming in an interview that He was subjected to “bullying”
and that “as long as ­these are normal, healthy kids it’s ­going to be fine for the
field and the ­family” (Cohen 2018, para. 6). At the end of 2019, He and his two
colleagues ­were sentenced to three years in prison and fined $430,000 for il-
legally practicing medicine by “knowingly violating [China’s] regulations
and ethical princi­ples with their experiments. . . . ​The court indicated that
three genet­ically edited babies have been born” (Kennedy 2019, para. 4).
Where w ­ ill the CRISPR path lead us? That is a key question pursued in
The Promise and Peril of CRISPR.

Before and ­After

Dr. He’s manipulation of the twin embryos has changed how scien-
tists and the public view CRISPR. Before his experiment, HGE was regarded
as verboten by numerous academies and scientists, at least u ­ ntil strict safe-
guards could be put in place. T ­ hese twins raise many questions about mov-
ing forward with germline editing. What was conceivable has been made real.
Meiosis is nature’s way of sorting and re-­sorting the genes of most living
organisms, guaranteeing diversity within species and driving evolution to se-
lect attributes—in the form of mutations—­that benefit the organism and
­favor survival. ­T hose mutations also inflict some individuals with painful,
life-­limiting ge­ne­tic syndromes. Some, like Tay-­Sachs, are lethal early in life,
and ­others, like Huntington’s, are ge­ne­tic time bombs. CRISPR can seek out
and destroy ge­ne­tic scourges, somatically and heritably.
We must address the ethical dilemmas CRISPR raises, particularly when
we begin to genet­ically tinker with the germline of ­human beings and any
other living plant or organism. Scientists, agronomists, and even dog and cat
breeders have been manipulating the germline of species for thousands of
years, but not u ­ ntil recently has it been pos­si­ble to do this in a specific gene-­
targeted way. CRISPR has drawbacks ­because it can cause off-­target muta-
tions, but newer CRISPR-­based tools, like prime editing—­“a versatile and
precise genome editing method that directly writes new ge­ne­tic information
into a specified DNA site”—­offer the possibility of avoiding the errors that
CRISPR can make (Anzalone et al. 2019, 149).
Considering ­these quickening advancements in CRISPR technology, we
have collected 16 essays in this volume devoted to investigating the trenchant
ethical issues that CRISPR poses. We have engaged renowned ge­ne­ticists, bio-
ethicists, and p ­ hilosophers to write about what they think are the most

Baer_CRISPR_int_4pgs.indd 4 05/03/24 1:22 AM

 Introduction 5

pressing questions CRISPR raises ­today. It is our sincerest hope that you w
­ ill
not only come away with a deeper understanding of CRISPR but that you
­will raise your voice in how it should be used in the ­future.

CRISPR: A ­Rose Bearing Thorns

The essays in this collection probe the challenging questions posed by
a gene-­editing tool that can cure agonizing diseases but can also give an
individual the power, as Esvelt (2019) warns, to “single handedly genet­ically
engineer a w ­ hole species” (2). Scarcely anyone would stop the promising cures
we have seen using somatic gene editing for sickle cell disease and other rare
ge­ne­tic blood, liver, and eye disorders—if the technology is safe, as has been
the case in the few diseases CRISPR has been used to treat. HGE is another
­matter and is the focus of this volume.
To systematically cover the multitude of ethical questions posed by using
CRISPR to edit germlines, we have divided the volume into six sections that
raise recurrent themes throughout:

Overview: The Era of CRISPR

Is it pos­si­ble to reconcile the dual uses of CRISPR technology?
How ­will our present-­day decisions about using heritable genome editing
affect the ­future when the ­future is not predictable?
What social, ­political, and economic forces drive the development of
CRISPR technology?

Ethical Questions
What are the dominant narratives that permeate discussions about CRISPR?
How ­ought we proceed in using HGE and who should be included in the
debate?

Personal Perspectives
Should HGE be used to edit disabilities and lethal ge­ne­tic syndromes, and
what constitutes a disability?
How might we understand a ­mother’s reproductive freedom versus a
fetus’s f­ uture health?

Diverse Voices
Who ­will be empowered to decide what ge­ne­tic features are deemed desir-
able or undesirable, and w
­ ill that further disenfranchise minorities?

Baer_CRISPR_int_4pgs.indd 5 05/03/24 1:22 AM

 6 The Promise and Peril of CRISPR

Should CRISPR technology be used to enhance one’s physical desires, say

in the case of trans individuals?

Dilemma of Controlling the ­Future

Should HGE be used in the exceedingly rare case when no other technol-
ogy exists to ensure that a child is biologically related to both parents?
What is the ­future impact of CRISPR on ­human variability?

Controls, Oversight, and Monitoring

Who should have authority over decisions about ­whether, when, and how
CRISPR should be used?
How might we oversee who has access to CRISPR to prevent its misuse?

Dual-­Use Technology: The Good, the Bad, and the Ugly

Chapter 1, by Rachel West and Gigi Gronvall, sets the stage with an
overview of the historical development of CRISPR technology, describing
“the expansion and refinement of CRISPR as a ge­ne­tic engineering tool.” The
authors then pre­sent a discussion of CRISPR’s dual use, “that, in addition to
its numerous benefits, it also has the potential to be misused and could lower
technical barriers to biological weapons development.”
Considering the challenges of CRISPR’s dual use, West and Gronvall out-
line “potential biosecurity concerns; and [recommend] steps governments
and scientists may take to reduce biosecurity risks.” They note that we must
come to terms with the possibility that CRISPR could be used for nefarious
purposes, where a rogue scientist or highly trained amateur could “edit an
existing pathogen to make it more damaging, edit a nonpathogenic organ-
ism to incorporate pathogen genes and traits, and even, theoretically syn-
thesize a novel pathogen.” In light of ­these risks, and that “­there are no
‘total’ solutions that can reduce the risks of misuse to zero,” the authors of-
fer safeguards and “partial solutions” that governmental agencies, science
academies, health governance o ­ rganizations, and companies dealing with
DNA sequences can put in place to mitigate catastrophic scenarios. A good
place to start, as several of our authors point out, is in high school and college
classrooms and in do-­it-­yourself (DIY) community labs, by embedding eth-
ics discussions into the science curricula and instruction (discussed in this
volume by Heinrich and Jorgensen). The goal is encouraging students to de-
velop and nurture the habit of thinking about ethics along with biosafety
(Karoff 2019).

Baer_CRISPR_int_4pgs.indd 6 05/03/24 1:22 AM

 Introduction 7

The Stories We Tell

How we think about CRISPR is determined by many social, cultural,
­ olitical, and economic ­factors. Scientists and physicians tell stories differ-
p
ently from individuals without the experience of researching ge­ne­tic
syndromes or treating patients suffering from them. Marcy Darnovsky and
Katie Hasson encourage us to refocus our conversations about CRISPR to “ex-
plore the considerable misrepre­sen­ta­tions and distortions that skew public
understanding” and to “foster constructive conversations about [HGE] and
make sure they are considered in consequential decision-­making pro­cesses.”
They point out that one prob­lem with the stories we tell is that they are
often infused with emotion that “shapes our thinking about how gene-­
editing tools should and should not be used.” Terms like designer and
CRISPR babies can evoke images of monsters or enhanced superhumans that
“distort understandings of how, by whom, and to what ends HGE might be
used.” We must also be wary of personal anecdotes. Though often power­ful,
they can be misleading. Darnovsky and Hasson relate the story of a m ­ other
speaking at the First International Summit on ­Human Gene Editing in
2015, whose child died in infancy. She pleaded for HGE to move forward to
save the lives of babies like hers. In real­ity, her baby suffered from anen-
cephaly, which had “no clear ge­ne­tic basis,” yet that moving story was
quoted numerous times in the media.
With so many stories being told about CRISPR, particularly why we
should and should not move forward with HGE, Darnovsky and Hasson
maintain that it is essential to “develop robust forms of public engagement”
that should include “­women’s health advocates, disabled ­people and com-
munities, and t­hose working to reduce economic and racial inequalities,”
along with “scholars from the humanities and social sciences.” One might
add theologians, ­philosophers, and anyone ­else who wishes to learn more
and hear about the prospects of ge­ne­tic engineering. In this volume, we also
bring in the voices of two bioethics scholars: one, a member of an Indige-
nous community and the other, a transfeminist. As members of the h ­ uman
community, we all should have a say in how CRISPR should be used. Bring-
ing all parties to the ­table requires what I call innovative conversations.
To date, the debate on CRISPR and germline genome editing has been
­limited to scientific socie­ties and bodies, with ­little public discussion among
­political candidates or from the White ­House. A topic as critical to our ­future
must be discussed by every­one, not just experts. “Genuine inclusivity in ­these

Baer_CRISPR_int_4pgs.indd 7 05/03/24 1:22 AM