Download The Center for Bioethics Cedarville University

Gene Editing: Reinventing Humanity?
Dennis M. Sullivan, MD, FACS, MA (Ethics)
Director, Center for Bioethics
Cedarville University
www.cedarville.edu/bioethics
E-mail: [email protected]
Learning Outcomes:
Participants will be able to:
1. Describe the new technologies for
gene editing.
2. Explain the difference between
somatic and germline genetic
treatments.
3. Explore the major ethical concerns
that these technologies raise.
A GENETICS BREAKTHROUGH:
CRISPR / CAS9
It’s Called CRISPR (Huh?)
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Clustered regularly-interspaced short
palindromic repeats
Segments of prokaryotic DNA
containing short repetitions of base
sequences
The short repetitions are palindromes
(e.g., “Madam, I’m Adam”)
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Part of a bacterial immune system
CRISPR is a “Repurposed Tool”
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Novel insight:
– CRISPR is a defense mechanism in
bacteria.
– Repurposed as a gene-editing
technique.
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By delivering the Cas9 protein and
appropriate guide RNAs into a cell,
the organism's genome can be cut at
any desired location.
Then new DNA can be added.
Who Discovered All This?
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(1987) Yoshizumi Ishino found the CRISPR
gene.
Eugene Koonin showed its purpose.
Emmanuelle Charpentier identified Cas9 and
guide RNA.
(2014) Jennifer Doudna determined the
mechanism and created the CRISPR/Cas9
system for gene editing.
(Doudna may end up getting the Nobel Prize)
GENE THERAPY IN THE PAST
Somatic Cell Gene Therapies
Alteration of genes of a diseased
individual, using a viral vector:
Candidate Diseases for Gene Therapy
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Single gene defects more likely to respond
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1990s: gene therapy approved for:
– Severe combined immune deficiency
(SCID)
– Familial hypercholesterolemia
– Gaucher's disease
– Cystic fibrosis
Example of a Somatic Cell Therapy
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Example: Cystic Fibrosis (CF)
– CF is due to a malfunctioning gene that codes for a bronchial
protein (in the lungs).
– The protein is responsible for fluid balance.
– Therefore, affected patients get think mucus plugs, eventually
causing an early death.
•
Gene Therapy for CF
– Insert a normal gene into the DNA of cells in order to
compensate for the nonfunctioning defective gene.
– Use a virus that normally causes colds.
– Result: lungs function better for a few months.
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Problems:
– Treatment is dangerous, complicated, and expensive
– If it works, benefit only temporary (altered cells are eventually
replaced by the defective cells once again)
THE ADVENT OF CRISPR/CAS9
A New Ballgame:
Though not yet ready for
clinical use, CRISPR / CAS9
allows direct editing of the human
genome
• Tested (so far) only in the lab
• Much higher accuracy than viral
vectors
• Fewer risks of unwanted side effects
•
THE CONTROVERSY
What Chinese Researchers Did:
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Used CRISPR/CAS9 on human embryos
for the first time (with beta-thalassemia)
“Tripronuclear zygotes” = polyspermic
embryos (one ovum, two sperm), therefore
non-implantable
What Chinese Researchers Did (cont.)
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A completely unnecessary trial (no new
knowledge gained)
Because all of this had already been done
in an animal model
86 human embryos  28 showed
evidence of “splicing”  only 4 had the
desired changes (many “off target” effects)
Therefore, the accuracy was < 5%.
THE ETHICAL CONCERNS
Utilitarian Concerns:
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The technique is “not ready for prime
time:” many errors, many possible bad
outcomes. YET:
Human Fertilization and Embryo Authority
in the U.K. has approved using CRISPR
in human embryos up to 14 days - as
long as they are not implanted.
Commodification of embryos
BBC Interview
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Kathy Niakan: Scientist makes
case to edit embryos
Wants to use the technique to
study human fertility issues.
(LINK)
Germ-Line Interventions
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Alter an individual’s entire genome,
including reproductive cells. These
changes could be passed down to
subsequent generations.
Consent is impossible to obtain
Unwanted and unpredictable side
effects are likely
Are we “playing God,” and meddling
with human nature and human dignity?
Stephen Pinker (Harvard Psychologist)
Given this potential bonanza, the primary
moral goal for today’s bioethics can be
summarized in a single sentence:
Stephen Pinker (Harvard Psychologist)
Given this potential bonanza, the primary
moral goal for today’s bioethics can be
summarized in a single sentence:
Get out of the way.
Stephen Pinker (Harvard Psychologist)
Given this potential bonanza, the primary
moral goal for today’s bioethics can be
summarized in a single sentence:
Get out of the way.
“A truly ethical bioethics should not bog down
research in red tape, moratoria, or threats of
prosecution based on nebulous but sweeping
principles such as ‘dignity,’ ‘sacredness,’ or
‘social justice’” (Boston Globe, September 31,
2015).
Therapy v. Enhancement:
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It seems reasonable to eliminate genetic
diseases:
– Sickle-cell anemia
– Huntington’s Disease
– Cystic Fibrosis
But the new technology may permit human
enhancement:
– “Designer babies” selected for sex, eye
color, or intelligence.
– Is there a fixed human nature, or can we
meddle with it?
WHAT ABOUT GOD’S
PERSPECTIVE?
Psalm 139:13-14a
For You formed my inward parts;
You knitted me together in my mother's
womb. I praise You, for I am fearfully
and wonderfully made . . .
Genesis 1:27
So God created man in his own image,
in the image of God he created him;
male and female he created them.
How Should Christians Respond?
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Be informed:
– Be skeptical of new technologies
– Some major advances come at a great
cost
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Get involved:
– Advocate for the sanctity of human life
– Especially help our younger generation,
who are so used to modern technologies
– Human life is precious, not a product
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Pray
Gene Editing: Reinventing Humanity?
Dennis M. Sullivan, MD, FACS, MA (Ethics)
Director, Center for Bioethics
Cedarville University
www.cedarville.edu/bioethics
E-mail: [email protected]