embryonic stem cells

Orthodoxy and Pastoral
Issues: Beginning of Life
Gayle E. Woloschak, PhD DMin
Northwestern University School of Medicine
Zygon Center for Religion and Science, Chicago
Technology Issues
Surveys about Scientists
• Views of children: speak foreign language that no one can
understand, live underground, wear white coats even when they
sleep, wear glasses, don’t require food
• Views of adults: speak language no one can understand, are antisocial, have cured diseases but only the rich people can get the cures
Science Impacts Humanity:
• Understanding the world—education
• Medicine—diagnosis, treatment, quality of life, end of life
• Ecology—recombinant foods, environmental issues
• Genome science—genetic counseling, gene editing
• Stem cells—new therapies, cloning
Example: Science drives the Ethics for HIV
• Early considerations: quarantine, restrictions for interactions
(including aid to those infected)
• Science demonstrated route of viral transmission
Result: Informed decisions
• Knowledge gained from science impacted decisions so they could be
made ethically.
• Inclusion of scientists in discussions was important, made decisions
timely and informed.
• Facts shaped the understanding of the disease…and therefore the
ethical treatment of patients.
“…science is a way of knowing, but it is not the only
way. Knowledge also derives from other sources,
such as common sense, artistic and religious
experience, and philosophical reflection.”
Francisco Ayala (population geneticist, NAS member)
in Theology and Science, 2003, 2:9-32
How Far is too Far? (or: Should we Limit
Technology?)
• New technologies are providing us with tools to manipulate the
environment, nature, energy, etc.
• Rapid movement from technology to discovery—makes it hard to
limit the technology
• Most limitation is done at the level of the application of the
technology
• Safety issues associated with technology take second-place
• Long term effects rarely considered or conceptualized
• Positive and negative aspects to application of technology
Concerns about Technology and our Society
 Conviction among general population that technology
can cure all things afflicting humanity
 Belief in technology over a belief in God
 Little pause for reflection in culture about whether a
technology should be used
 Little testing of whether a technology is safe
 Result: Attitude of entitlement, disappointment, high
costs for medical intervention
Technology that is Available
• Science and engineering are technology-driven.
• Those that can use new technologies are the “can-dos” and ultimately
become the “haves”
• Those that don’t explore new technologies rapidly become obsolete.
• Examples: cell phones, computers, earthquake-safe buildings, etc.
On Medical Knowledge as a Gift from God
“Medicine is a gift from God even if some people do not make the right
use of it. Granted, it would be stupid to put all hope of a cure in the
hands of doctors, yet there are people who stubbornly refuse their
help altogether.”
“All the different sciences and techniques have been given us by God to
make up for the deficiencies of nature…Not by chance does the earth
produce plants that have healing properties. It is clearly evident that
the Creator wants to give them to use to use.”
-St. Basil, The Greater Rules, 55
On the Source of Knowledge
“For it is he (God) who gave me unerring knowledge of what exists, to know the
structure of the world and the activity of the elements; the beginning and end
and middle of times, the alternations of the solstices and the changes of the
seasons, the cycles of the year and the constellations of the start, the natures of
animals and the tempers of wild animals, the powers of spirits and the thoughts
of human beings, the varieties of plants and the virtues of roots; I learned both
what is secret and what is manifest, for wisdom, the fashioner of all things,
taught me.”
-Wisdom of Solomon 7:17-22
Orthodox Perspectives on Technology
 Technology can be good or bad depending on how it is used—
ex/radiation
 Wisdom and creativity are gifts from God
 Medicine and medical intervention are appropriate for
humanity because they are gifts from God
 Knowledge should not be blinded by self-importance or be bent
on self-perpetuation
 Must know how to act when needed and abstain when
appropriate—when to act, when to “let it be”
Human Responsibility
• Technology comes with a responsibility: to oversee it properly, to
protect those who might be harmed by it (including the earth and
animals)
• Must exert proper stewardship over technology
• Must try to be humble – it is not possible to imagine all consequences
of a technology – being watchful and willing to accept truth is
necessary
• Must use discernment: eliminating technology means the elimination
of cures; accepting all technologies will leave ethical concerns
Beginning of Life and IVF
Newly fertilized egg
3rd day embryo in mouse: 16 cells,
beginning of implantation
FIGURE 12.3 During preimplantation, the embryo
consists of a limited number of cells. A: Newly fertilized
mouse egg. B: By the 3rd day, the mouse embryo
consists of only 16 cells. About 5 days after conception in
the mouse, which corresponds to about 9 or 10 days in
the human, the embryo becomes embedded in the wall
of the uterus, and at about this time, cells begin to
differentiate to form specific tissues and organs.
(Courtesy of Dr. Pedersen, University of California at San
Francisco.)
In Vitro Fertilization (IVF)
• Used primarily to treat fertility “disorders”: help infertile couple bear
children
• Originally called “test-tube babies”
• Approach: isolate eggs from mother, sperm from father, mix in the
test tube, let the embryo develop for several days and then implant
into the mother
• Left over fertilized eggs in test tube can then be used for embryonic
stem cells
How are IVF-embryonic stem cell lines
established?
• IVF-generated fertilized eggs are grown in culture using “feeder cells”
from mice to provide growth factors.
• The process is inefficient and not all cells established in culture will
become an embryonic cells cell line.
• Once a line is established it is tested for 2 features: absence of
genetic abnormalities (hard to measure) and ability to grow without
developing into any set (partially mature) cell type.
• Cells are then harvested and frozen for future studies.
Standard Laboratory for
Stem Cell Studies
Embryonic Stem Cell
Why IVF and not adoption?
• Many question whether IVF is based in the need to pass “my genes”
on to the next generation rather than care for a child to be raised.
• High costs of adoption, difficulty of adoption, problems with
enculturation are issues raised by those who choose IVF.
• IVF is also expensive
Unique Aspects of IVF: Manipulation of the
Embryo (PGD)
• Pre-implantation Genetic Diagnosis
• Selection against certain genetic defects
• Selection for an embryo that produces certain proteins
• 2009: Clinic in LA offers screening for gender and physical traits
Pre-implantation Genetic Screening
Nature 445, 479-480
Reproductive medicine: The first cut
Religious Perspectives: Roman Catholic
Two major issues:
1. Strong opposition to IVF: IVF eggs are embryos despite their not
having been in the womb (based on Encyclical Letter of Pope John
Paul II, 1995)
2. Opposition to separation of sexual and procreative act (Vatican,
1993)
Other Religious Perspectives
• Supportive of IVF/stem cell research: Jewish, Anglican, some
Lutheran, Presbyterian, others
• Opposed: Southern Baptist, National Association of Evangelicals
Orthodox Christians and Sanctity of Life
• Strong belief in the sanctity of life
• Do not have same attitudes toward procreation as the Roman
Catholic Church
• Do have a general acceptance of technologies that preserve and
protect life provided that it does not extend meaningless life
• Major questions: (1) does the Orthodox Church accept IVF and (2)
are the IVF-generated embryos human life?
Orthodox Attitudes Toward IVF
Contradictory
• Some bishops have given a blessing for a married couple who cannot
have children to use IVF to assist them.
• This is done on a case-by-case basis.
• It is not clear what the bishops thought about the remaining IVFgenerated embryos.
• Other bishops have refused to give a blessing. The Church of Russia
has not sanctioned IVF. The Church of Greece has been more
ambiguous.
Stem Cell Research
What are Stem Cells?
• Stem cells are immature cells that under the right conditions can be
induced to give rise to mature (differentiated) cells.
• Two types of stem cells: adult and embryo
• Applications for adult stem cells: bone marrow transplants, blood
transfusions; other applications have not proven successful
• Applications for embryonic stem cells: currently banned in the US
What are Embryonic Stem Cells?
• Currently being developed for use in human disease; difficult because
of potential for graft rejection
• Concept: Some diseases lead to loss of cell function. Can we replace
lost cells with embryonic stem cells?
• Possible applications: diabetes, Parkinson Disease, Alzheimer
Disease, spinal cord injury, others
Lisa M Hoffman & Melissa K
Carpenter . Characterization and
culture of human embryonic
stem cells. Nature
Biotechnology 23, 699 - 708
(2005)
Lisa M Hoffman & Melissa K
Carpenter . Characterization and
culture of human embryonic
stem cells. Nature
Biotechnology 23, 699 - 708
(2005)
Pros and Cons of Embryonic Stem Cells
• Cons: Sacrifice of embryos cannot be justified; use of embryos for
stem cells could be used to “justify” abortions or even increase
abortion rates; embryonic stem cells can be rejected by the host
• Pros: Stem cells may cure many diseases for which there is currently
no treatment
• Solution: Obtain stem cells from other sources—some of these have
been successful and mitigate problems of graft rejection
Possible Sources of Embryonic Stem Cells
• Embryo—obtain stem cells from therapeutic abortions
• Cells remaining from IVF—fertilized eggs never implanted into a
mother
• Cloned cells—nucleus from adult cell transplanted into an egg cell
• Oocytes that have been induced to have 2 nuclei
Adult vs. Embryonic Stem Cells
ADULT STEM CELLS
• Used for decades: for example,
bone marrow transplants
• Orthodox Church has supported
their use
• Currently developed for
additional therapies including
cardiac diseases, with some
limited successes
• Reprogramming adult cells to
be stem cells for different
organs
• Can match for compatibility
from one person to another
much like transplantation
EMBRYONIC STEM CELLS
• Derived from other sources: fetal
sources are NOT used; IVF is main
sources
• IVF-embryo stem cells use not
supported by Catholics and some
Protestants (groups against birth
control); supported by Judaism,
Episcopalian, Presbyterian, etc.;
Orthodox have not expressed a view
• Less limiting because embryonic
stem cells develop into many cell
types; more promising clinically
• Experimental: no applications now
• State limitation: transplantation
Scheme for iPS Generation from Adult Cells
Introduce virus
to express stem
cell genes
Isolate donor cells
Add in feeder cells that
are “inactivated”
Small subset of cells
become iPS and
generate ES-like
colonies
Pros and Cons of induced Pluripotent Stem
Cells (iPSCs)
• Cons: Requires reprogramming of adult stem cells to be pluripotent:
low efficiency, genomic insertion comes with risks, can go on to
develop tumors, incomplete reprogramming sometimes occurs
• Pros: does not need embryonic cells, do not need to worry about
graft rejection
• Some risks may be mitigated with newer technologies: gene editing is
being improved, work with improved viruses as vectors may reduce
cancer risks
Orthodox Perspectives
• Opposed to use of embryos for stem cells
• Perhaps opposed to the use of cells remaining from IVF—
questionable
• Questions about cloning- and oocyte-derived stem cells
• Current discussions by several Orthodox groups
• No opposition to use of stem cells that are NOT derived from stem
cells (but this is not well-discussed)
Technologies and Pastoral Care
• Biotechnologies increase the number of decisions and turning points in life.
• Challenge for pastors is to be equipped with sufficient understanding and insight
to help individuals, couples, families address these issues.
• Examples: marriage/pregnancy when genetic issues arise; guilt or blame or
denial in decisions when a genetic condition results; questions about new forms
of contraception, conception, and beginning of life questions.
• Requires more collaboration between pastors and health professionals.
Genetic Counseling and
Pregnancy
Genetic Counseling During Pregnancy
• Often use small amount of amniotic fluid to examine genetics of the
child (15-20th week of pregnancy)
• Purpose is not always for aborting the child—can be to prepare the
family for a difficult birth, treat the child at birth for a disease or
abnormality, etc.
• Risk of amniocentesis is 0.06% or lower
Some diseases diagnosed by amniocentesis
• Down Syndrome (Trisomy 21)
• Trisomy 13, Trisomy 18
• Fragile X Syndrome
• Neural tube defects (spina bifida, anencephaly)
• Other rare inherited disorders
• Prediction of fetal lung maturity
Site for amniocentesis
Amniotic fluid:
Perform amniocentesis under ultrasound guidance
Insertion of the needle
Orthodox Perspectives on Amniocentesis
• Motivation is important
• Appropriate motivations: to prepare the family for the coming child
(particularly if a physical abnormality is predicted for birth), to help
the child at the time of birth
• Inappropriate motivations: abortion of a child
• Motivations that involve selection of particular traits in children (male
vs female) would not be considered acceptable
Gene Editing
What is CRISPR and what does it do?
• CRISPR-Cas9 is a protein – nucleic acid complex that
can be used to snip DNA at the precisely determined
location
• Why is that impressive?
• There are billions of possible addresses for DNA
cutting in a genome – CRISPR advances genome
editing by leaps and bounds.
• CRISPR gives more precise cleavage and insertion with
fewer off-target effects
Cell. 2014 Feb
27;156(5):935-49.
EcoRI cuts DNA
What sequence will be
cut?
GTATAC
Repeated thousands of
times in a genome
Probability of a correct
replacement “fix” occurs
is miniscule; wrong “fix”
can cause cancer.
By Boghog2 - Own workThis
image was created with
PyMOL, Public Domain,
https://commons.wikimedia.
org/w/index.php?curid=9027
117
Structure of the homodimeric restriction enzyme EcoRI (cyan
and green cartoon diagram) bound to double stranded DNA
(brown tubes).[37] Two catalytic magnesium ions (one from
each monomer) are shown as magenta spheres and are
adjacent to the cleaved sites in the DNA made by the enzyme
(depicted as gaps in the DNA backbone).
CRISPR cuts DNA
What sequence will be cut?
A target that is 20 nucleotides long and may be UNIQUE in the
genome. Majority of “fix” events that happens will happen at a
correct place!
A CRISPR-Cas9 targeted double-strand break. https://www.thermofisher.com/us/en/home/li
Cleavage occurs on both strands, 3 bp upstream fe-science/genome-editing/genome-editingof the NGG proto-spacer adjacent motif (PAM) learning-center/crispr-cas9-technologysequence on the 3’ end of the target sequence. information.html
Improving accuracy: Engineered high-fidelity
CRISPR-Cas9 with no detectable off-target effects
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Kleinstiver BP,
Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Keith Joung J. Nature. 2016 Jan 6. doi:
10.1038/nature16526.
Developing programmable shut-off: Developing
inhibitors of Cas9
Naturally encoded
CRISPR/Cas9 inhibitors
efficiently block genome
editing in cultured human
cells providing a much
needed “off-switch”.
Pawluk, A., et al., Naturally Occurring Off-Switches for CRISPR/Cas9. Cell 167, 1829-1838 (2016)
DIY CRISPR cloning kit $150
Josiah Zayner was a postdoc at NASA when
he first started thinking about do-it-yourself
biology. Using crowdfunding, Zayner raised
$71,036 by December 2015 and created The
ODIN. The ODIN now sells genetic
engineering kits, such as the CRISPR kit, that
contain everything one needs to perform a
sample experiment. With a full-time staff of
four, Zayner and his team make the
components of the kit or purchase them
from overseas wholesale manufacturers;
they then assemble the boxes in Zayner’s
Palo Alto garage and mail them to
customers.
http://www.biotechniques.com/news/biotechniquesNews/biotechni
ques-365397.html#.WLr_DBIrJqx
In US…
•
•
•
•
•
•
•
There was some interest in a moratorium on use of CRISPR-cas9
Many scientists called for a “world-wide moratorium”
Top scientists called it “essential”
In DC, an international summit was held (including EU and Asian countries):
1. Basic and preclinical research: necessary
2. Clinical use somatic cells: promising
3. Clinical use germline: great potential but risk because of potential offtarget effects, implications for future generations, could lead to permanent
genetic “enhancements” and more
• 4. Need for continued discussion….
Heritable Genome Editing Perspectives (NAS
report)
• Advantages: Preventing transmission of inherited disorder; treating
diseases that affect multiple tissues
• Limitations: Mosaicism; alternative routes to heritable edits (sperm
precursors, e.g.); effect on the human gene pool
• Ethical concerns: Balancing individual-level and societal-level benefits
(cures vs. unintended risks); natural vs edited genome; human dignity
vs. fear of eugenics; economic and social justice; slippery slope
Orthodox Perspectives
• No discussion on gene editing is on-going
• Several panels exist among non-Orthodox Christian groups: Lutheran,
Anglican/Episcopalian, Presbyterian in US
• THERE NEEDS TO BE DISCUSSION ON THIS!! It will become a pastoral
issue.
Concluding Thoughts
Technology in the Light of Humility: Job 38
• 4 “Where were you when I laid the foundations of the earth? Tell me, if
you have understanding. 5Who determined its measurements? Surely
you know! Who stretched a measuring line across it? 6On what were
its bases sunk, or who laid its cornerstone— 7 when the morning stars
sang together and all the sons of God shouted for joy?
• 8 Or who shut up the sea behind doors when it burst forth from the
womb, 9 when I made the clouds its garment and thick darkness its
swaddling band, 10 and prescribed bounds for it and set its bars and
doors, 11 when I said, ‘This far shall you come and no farther; here is
where your proud waves be stayed’?
• 12 “Have you ever given orders to the morning, or shown the dawn its
place, 13 that it might take the earth by the edges and shake the
wicked out of it? 14The earth takes shape like clay under a seal; its
features stand out like those of a garment. 15The wicked are denied
their light, and their upraised arm is broken.
• 16 “Have you journeyed to the springs of the sea or walked in the
recesses of the deep? 17 Have the gates of death been shown to you?
Have you seen the gates of the deepest darkness? 18 Have you
comprehended the vast expanses of the earth? Tell me, if you know all
this.
Humility
• No technology should be used primarily to exalt the achievements of
humanity or to prove human ”mastery” over death, disease and
aging.
• Through science we may seek to gain knowledge about God’s
creation, but we must realize the limits of our comprehension and
utter impossibility of applying our cognitive powers to an
understanding of God that penetrates to the depths of His Being.
• Nevertheless, if humans develop the ability to treat a disease with
technology, it should be viewed as a gift from God.
Humans as Microcosm and Mediators
“Because the human person is both microcosm and mediator,
unifying the creation and offering it back to God in thanksgiving
— because more particularly, we humans have the ability
consciously and by deliberate choice to modify and refashion the
world — there is imposed upon us a grave and daunting
responsibility. The fact that we are made in the divine image and
so endowed with freedom — creators after the image of God the
Creator — carries with it a terrible risk. We can use our creative
power both for good and for evil. We can illumine and
transfigure, but equally we can pollute and destroy.”
-from Bishop Kallistos (Ware) or Diokleia, “Through the Creation to the
Creator”
Metropolitan Anthony of Sourozh:
“Our task is not merely to imitate what was done by the saints of
previous eras, but somehow to appropriate at a much deeper level
the way in which they engage their own historical environment,
seeking to respond as they would have responded had they lived in
our day.”