Bioethics: Some Cases in Point WV Wednesday

Bioethics: Some Cases in Point

WV Wednesday

Jon T. Holmlund, M.D.July 8, 2015

Contains images from internet: slides for personal educational use only, not for dissemination

To begin, some disclaimers…

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Outline

• What is bioethics? Brief historical/philosophical background

• How to look at technology• A trip to a bleeding edge • Discussion

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What is “bioethics”?

• The effort to determine how we ought to live in matters concerning:– Medicine– Living things in general– Biology and its applications

• Current “crisis” issues reflect flaw in modern liberal, technological society– Pre-eminence of the individual– Mastery over nature

Genesis of Modern Bioethics• Human Subject Protection

– Research– Reaction to Atrocities

• Allocation of Scarce Resources– Kidney Dialysis (1960’s)

• Definition of Death– Artificial Ventilators, Heart Transplantation

• Christians (esp. Roman Catholics) prominent initially• More secular with cultural drift in pluralistic society• Ever-expansive agendas

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Ethical Theories• Deontological (duty: Kant)• Utilitarian—”greatest good for greatest number”

– More refined: “consequentialism”• Natural Law—”written on the heart” (Aquinas and

others)• Divine Command Theory (special revelation, role

of elders)• Virtue Ethics (MacIntyre)• Other takes—feminist ethics, environmental ethics

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Principalism (Belmont Report, 1978)An ethical lingua franca in a pluralistic society

• Respect for persons– Acknowledge autonomy– Protect those with diminished autonomy

• Beneficence– Do not harm (“non-malificence”)– Maximize benefits/minimize harms

• Justice– Fair distribution and justification for inequality

Note: Principles not hierarchal; Arrived at by casuistry

(Some) Limitations of Principalism

• Best suited to biomedical research• Lacks strong theoretical foundation• Open to some criticisms of utilitarianism• Limits of casuistic reasoning

– Agree, but can’t say why (Belmont, EU on human dignity)– Reliance on paradigm cases– Appears to ground “ought” on case facts– Lacks “certitude”– Potentially relativist OR culture-centric

John Rawls (1921-2002)

– A Theory of Justice (1971 and later)– Public discourse must proceed behind a “veil”

where no religious perspectives are permitted and metaphysics are generally suspect

– Leads to a “constructivist” view• Attempt to achieve consensus about what we think

the case is—rather like law in one sense, science in another

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Public Policy Discussions Under Principalism

• Consequentialist• Constructivist

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Moral Realism

The position that when we say “we ought [not] do X,” we assert a

fact about the world

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The Expanding Scope of BioethicsSTAGE EXAMPLES ISSUES EVANGELICAL STANCE?

Bioethics 1“taking life”

AbortionEuthanasiaEnd-of-life care

Who is human?Who is alive?Can human life be deliberately taken?

Christian alternativesCulture war“Call your congressman”

(Largely settled positions?)

Bioethics 2“making life”

In vitro fertilizationGenetic diagnosis of embryoSperm/egg donationSurrogate momsCloning (“2.5?”)

Reproductive freedomMaking child to orderRe-defining the family“Making vs begetting”Children as gifts vs projects

Unease and alarm -BUT-Freedom or acceptance in some cases

(Need for pastoral input in some personal choices)

Bioethics 3“faking life”

Synthetic biologyCyberneticsOther emerging technologies

Scope of human dominion Human nature itself; changing or even supplanting

Huh?????

(Arcane matters for experts; far off from common lives)

Nigel Cameron in Human Dignity in the Biotech Century, pp. 26-27

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Approaching bioethics as a Christian

• A branch of Christian ethics• Relative appeal to general vs special revelation

– Faith/reason; scripture/natural law; 2 kingdoms

We can think of a range of approaches

From To

Biblical scholarship(on the one hand)

Philosophical ethics(on the other)

See also VanDrunen, Bioethics and the Christian Life

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Bioethics—prevailing perspectives

“Secular bioethics only” •The prevailing view in society•Example: text by Beauchamp and Childress

“Christian bioethics only”

•Thinkers emphasizing special revelation or noetic effects of the Fall•John Frame/Van Tillians; maybe Barthians

“Secular and Christian bioethics identical”

•Certain Contemporary Roman Catholics (McCormick)•Arguments for Natural Law that try not to appeal to God --Criticized as “the second tablet project”*

“Secular and Christian bioethics radically different”

•H. Tristam Englehardt

“Secular and Christian bioethics distinct but legitimate”

•Edmund Pellegrino; Scott Rae (Biola U); Center for Bioethics and Human Dignity•Could fit other traditionally-minded thinkers (secular or other religions)

Categories from David VanDrunen, Bioethics and the Christian Life, pp.23-37.

*J. Budziszewski, The Line Through the Heart, especially chapter 2, pp. 23-40

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Whatever our approach…• These things are foundational:

– The God Who is there• “In Him we live and move and have our being”

– The sovereignty of God– The truth of the gospel and of Scripture

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The Christian’s “gospel orientation”

• Redeemed by Christ• Death defeated• New creation• Liberation from sin• Future conformity to Christ’s

likeness• “The aroma of Christ”• “Aliens and strangers”

• Great Commission• Love• Gratitude• Justice• Mercy• Reverence• Humility

The Indicatives then The Imperatives

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Anthropology—Secular View• Humans seem to be considered to

be:– Sophisticated machines

– OR –

– Fancy animals• “Soul”: a poetic metaphor for brain

function• Personhood can come and go

– Depending on capabilities at the time• Radical autonomy

http://media.photobucket.com/image/planet%20of%20the%20apes/lhernandez33/Planet.jpg?o=7

http://upload.wikimedia.org/wikipedia/en/0/09/DataTNG.jpg

“At the heart of liberty is the right to define one’s own concept of existence, of meaning, of the universe, and of the mystery of human life.”

Justice Anthony KennedyPlanned Parenthood vs. Casey, 505

U.S. 833 (1992

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Anthropology—A Theological View• Man is created in the image of God

– Essential: all human individuals– Communicable attributes of God– Unique privilege for humans in creation– Connection with and Reflection of God

(Kilner)*• A substantial, specifically human soul

– Distinct from but unified with the body– Survives physical death– “Ultimate capacities” (J.P. Moreland)*

• Essential to the sort of being man is– Religious, psychological, social,

(hetero)sexual, ecological, rational, and technological dimensions

• Every human being (from conception) an image-bearer

.J.P. Moreland, What is the Soul? Pp. 39-41John Kilner, Dignity and Destiny, 2015

A few words about technology

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How we usually think about technology• Morally neutral tools• Legitimately used under the “dominion

mandate” • “What’ll they think of next?”• What are morally good or bad are:

– Our goals– Our means to an end

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http://www.school-clip-art.com

Fine.What’s water?

How’s the

water?

OUR TECHNOLOGIES ALTER OUR MOST BASIC, UNSPOKEN ASSUMPTIONS ABOUT DAILY LIFE

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Some technologies fundamentally change our patterns of life:

In the 21st-century U.S. we tend to frame questions technologically*

*Neil Postman, Technopoly

Images from http://www.fg-a.com

“Studies show…”

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It’s easy to underestimate how much we depend on our technologies

Two things about technologiese.g., after Jacques Ellul

• They have a life of their own• They embody an idea

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Our technologies are often “two-edged”--

--or originated from the making of war--

http://www.symbiotekpodcast.com/wp-content/uploads/2010/03/smiley-nuclear.jpg

http://upload.wikimedia.org/wikipedia/commons/4/45/MtRedoubtedit1.jpg

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--and sometimes things bite back, through unintended consequences.

http://dummidumbwit.files.wordpress.com/2010/04/great_white_shark_south_africa6.jpg

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Range of responses to transformative technology

FROM TOGut reaction “Way cool” “Way gross”Feasibility “Nearfetched” “Farfetched”Intellectual Fascination RepugnancePersonal Involvement

Dive in/Sign up Leave to experts

Public Policy “Pro-actionary”* “Pre-cautionary”*

*Parens E, “Ethical Issues in Synthetic Biology”

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The common search for a reasonable middle

NOT NOR NORZzzzz…

Rather, do this:•Proceed prudently•Stewardship•Appropriate regulation•Moral/technical control and limits•Risk/benefit analysis•Justice—seek and ensure•Calm down/”don’t worry”•Trust our knowledge/experts•Maintain competitive advantage

http://www.gettyimages.com/detail/2014797

GO for it!

http://media.photobucket.com/image/rocky%20stallone/leprechaunbaby/stallone.jpg?o=2

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The “middle”: reasonable but elusive• Overconfidence in human knowledge• Overconfidence in human virtue• Inability to assess most extreme risks• Potentially smug and conflicted experts• Zero risk means paralysis: zero action

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Proceed in some way,

With caution,

makes sense, BUT--

There may be some things thatought NEVER be attempted

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A word about red lights…

• Is there any historical precedent for humans NOT pursuing a technology beyond some stated ethical limit?

• Have there ever been any boundaries that ought not be crossed, that were not? Any limits that have held?

• Can we expect to limit our human biotechnology to the treatment of known disease in existing individuals?

We should first ask what we should do…

But typically we are first confronted by what we can do,

as a fait accompli

What we can do is limited only by our imagination

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“Developments [in bioethics] tend to proceed from unthinkable horror to generally accepted

practice in the space of about 20 years”

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Richard Doerflinger, CBHD Annual Conference, 2014

From recent history to the bleeding edge

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On the Moral Status of the Unborn (After Kaczor, The Ethics of Abortion)

Principle CommentThe human person’s life begins at conception (fertilization)

Not after birth; all humans are persons

Not at birth; moral status (personhood) not a matter of locationNot between conception and birth; would depend on realized capacitiesAt conception: life of a constitutive human begins

Unborn human has rights from conception

Embryo is not just “a collection of cells”

It is wrong to abort a human person

Various objections try to pit mother’s rights against unborn, often by arguing pregnancy is an unintended imposition

Abortion not permissible in hard cases except if mother’s life in danger

The proper answer to the rape/incest question: One evil does not warrant commission of a second evil

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Two Perspectives on Childbearing

• Children are a gift to be received (within the context of biblical marriage)

• Children are a project—something to be obtained

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Born July 25, 1978

Born July 25, 1978Louise Joy Brown

IVF--Issues• Risks to baby• Fundamental separation of procreative and

unitive aspects of sexuality• Risks to mom• Egg donors: Risks, exploitation, payment• Child’s genetic heritage (if gametes donated)• Abortion, “eugenics”• “Excess” embryos• Undermining of adoption

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Some IVF statistics: 2010source: Centers for Disease Control and Prevention

• Total cycles: 100,869– 82,563 autologous– 18,306 donor– 40.6% used frozen embryos

• Donated eggs: – Average donor age 28 (almost all under 35)– Average recipient age 41 (25% over age 45—vs 13% autologous)– (Technology now exists for women to freeze own eggs)

• 24.4% “good perinatal outcomes”– Baby >37 weeks, >2500 grams (about 5 ½ lbs), single birth

• Single embryo transfer about 15% of the time– 2 embryos: 50-75%; others 3+

• 62.5% of pregnancies single, 36.7% twin– “Octomom” is NOT the rule

• Current recommendations moving toward single embryo transfer• Cost is high

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How do IVF babies do later in life?

• So far they appear to do well• No good data on:

– Relationship of outcome to IVF per se– Health beyond infancy

• Other species: IVF outcomes may be poor indeed (cattle)

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Procreative Contracting

• Unmarried adults desiring children• Sperm and Egg Donors

– Selves, Directed or Banked Donation, Stem Cell-Derived?

• IVF• Surrogate Gestator (Woman to Bear Child)

– Retains no rights post birth!– Paid medical costs

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So…

• Has IVF taken on a life of its own?• What idea does it embody?

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CMDA on Assisted Reproductive Technology (1 of 4)

• These principles should guide the development and use of assisted reproductive technologies:– Fertilization resulting from the union of a wife's egg and her

husband's sperm is the biblical design.– Individual human life begins at fertilization.– God holds us morally responsible for our reproductive choices.– ART should not result in embryo loss greater than natural

occurrence. This can be achieved with current knowledge and technology.

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CMDA on ART (2 of 4)• CMDA finds the following consistent with God's design for

reproduction:– Medical and surgical intervention to assist reproduction (e.g., ovulation-inducing

drugs or correcting anatomic abnormalities hindering fertility)– Artificial insemination by husband (AIH)– Adoption (including embryo adoption)– In-vitro fertilization (IVF) with wife's egg and husband's sperm, with subsequent:

a. Embryo Transfer to wife’s uterusb. Zygote intrafallopian transfer (ZIFT) to wife’s fallopian tubec. Gamete intrafallopian transfer (GIFT) to wife’s fallopian tube

– Cryopreservation of sperm or eggs

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CMDA on ART (3 of 4)• CMDA considers that the following may be morally

problematic: (!)– Introduction of a third party, for example:

• Artificial insemination by donor (AID)• The use of donor egg or donor sperm for:

– In-vitro fertilization– Gamete Intrafallopian Transfer– Zygote Intrafallopian Transfer

– Gestational Surrogacy (third party carries child produced by wife’s egg and husband’s sperm)

• CMDA allows exception if wife unable to gestate

– Cryopreservation of Embryos• Intent that all embryos transferred to genetic mother some time in future• Limit number of embryos• All frozen embryos transferred to genetic mother, adopted, or carried by

gestational surrogate (!)51

CMDA on ART (4 of 4)• CMDA opposes the following procedures as

inconsistent with God's design for the family: – Discarding or destroying embryos– Uterine transfer of excessive numbers of embryos– Selective abortion (i.e., embryo reduction)– Destructive experimentation with embryos– True surrogacy (third party provides the egg and gestation)– Routine use of Pre-implantation Genetic Diagnosis– Pre-implantation Genetic Diagnosis done with the intent of

discarding or destroying embryos.

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A Brief Segue Into Molecular Biology…

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Gene Mutations• Can cause, or increase risk of, disease• Naturally occurring or environmentally induced• Different kinds of mutations• Some diseases caused by simple mutations of

single gene (Huntington’s disease, Sickle Cell Anemia)

• Others caused by more complex processes (most cancers)

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Preimplantation Genetic Diagnosis (PGD)

• On a single cell• Taken 5-6 days (8 cells total) after fertilization• Results in 24 hours• Diagnostic error rate: 0.7%• Cost: $2500 and falling• Reduces risk of recessive genetic disease from

25% to <1%• “Most” embryos do well• 2010: >47,000 PGD babies in US

58Source: Mark Hughes, MD, presentation at ASH, 2011

Sickle-cell Anemia• Abnormal hemoglobin/reduced oxygen-carrying• “Point” mutation (single “letter of DNA”)• Relative protection against malaria• Recessive

– Need 2 copies of the mutation to have disease– Carrier state—generally not affected by disease– 25% risk of disease in offspring of 2 carriers

• U.S.: most common in African-Americans• Spectrum of clinical illness• Treatment: high-dose chemo/BMT

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The Boozer Case• First born, Carmani: bad SCA• Conceived a “savior sibling” via IVF and PGD

– Needed to create 16 embryos to get one with no sickle mutation and with immunologic match for BMT

– That one implanted into Mom• ?Fate of the others?

– At birth: harvest cord blood for BMT– Big brother: cured of disease

• Cf. “Boozer’s Buddies Foundation”

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Play “60 Minutes” Segment here

http://www.cbsnews.com/news/breeding-out-disease-with-reproductive-genetics/

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Rewriting the Code of Life:The Policy Implications of Human Genome

Editing (CRISPR/CAS9)

Acknowledgment to: Michelle Crotwell Kirtley, PhD Bioethics & Public Policy Associate at The Center for Bioethics & Human Dignity

CRISPR/CAS9: What is it?

https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology

http://www.theberkeleygraduate.com/2014/10/attack-of-the-gene-drives/cas9_green-01-1024x1024/

Why is CRISPR/CAS9 so revolutionary?

• Cheap, easy to use, efficient.

• Prior to the development of CRISPR, it was difficult, expensive and time consuming to create animals with targeted mutations.

• Earlier generations of genome editing technology are more difficult (and expensive) to use. (TALENS, Zn++ finger nucleases, RNAi).

CRISPR/CAS9 applications: Food production

For food that relies on starter bacterial cultures (yogurt, cheese), infection of the needed bacteria can wipe out an entire culture, ruining large batches of product. CRISPR confers resistance to infection, protecting bacterial starter cultures from infection.

CRISPR/CAS9 applications: Lab tool

CRISPR/CAS9 used to introduce or correct mutations in crops or livestock.

– Distinct from GMO (genetically modified organisms) food because CRISPR-modified organisms don’t contain foreign DNA or “transgenes.”

• USDA has already ruled that organisms modified with prior generation editing techniques (TALENS or Zn finger nucleases) do not require special approval because they do not involve the use of “plant pests” to introduce changes to the plant’s DNA.

– Cibus has become first company to bring a CRISPR-modified product (herbicide-resistant Canola) to the market.


• Precise gene targeting in cynomolgus monkeys. The FIRST targeted gene disruption in primates .

• Two genes modified at the same time.Cell 2014 156, 836-843DOI: (10.1016/j.cell.2014.01.027)

Copyright © 2014 Elsevier Inc. Terms and Conditions

CRISPR/CAS9 applications: Lab Tool

• Scientist showed that a mutation associated with tyrosinemia, a human metabolic disease, could be corrected in adult mice using CRISPR/CAS9.

• Scientists have used CRISPR/CAS9 to excise HIV from the DNA of human cells.

• Researchers have corrected a mutation that causes -thalassemia in induced pluripotent stem cells (iPS cells) that are then differentiated into hematopoietic stem cells.

http://www.nature.com/nbt/journal/v32/n6/full/nbt.2884.html


CRISPR/CAS9 can be used to modify gene expression.

http://www.cell.com/cell/abstract/S0092-8674(14)01178-7

• Can be used to study the “dosage” effects of various genes.

• Can be used to observe and understand conditions under which genes of interest are turned “on” or “off” or whose expression is turned “up” or “down.”

• Can be used to identify cells and tissues in which a certain gene is active, not only in cells lines but in whole organisms, in real time during development.

CRISPR/CAS9 applications: Gene Drives

A modification of the CRISPR/Cas9 system allows a mutation introduced on one chromosome to be copied to the partner chromosome in every generation.

• Could be used to eliminate vector-borne diseases such as malaria and yellow fever.

• Could have unforeseen ecological effects.

• Mutations in the guide RNA over time could cause unintended regions of the genome to be edited. These “off-target” mutations could then overtake the population.

• “[Gene drives] have to have a fairly high pay-off, because it has a risk of irreversibility — and unintended or hard-to-calculate consequences for other species,” says George Church, of Harvard Medical School.http://blogs.scientificamerican.com/guest-blog/gene-drives-and-crispr-could-

revolutionize-ecosystem-management/

Or IVF embryo

Future generations

Heritable

CRISPR for Gene Therapy?

CRISPR/CAS9 applications: Gene Therapy?

• CRISPR/CAS9 could be used to correct mutations in human adult stem cells or iPS cells. In theory, the edited cells could be transplanted back into the patient to treat diseases such as HIV and Fanconi’s anemia.

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00455-X

Target HIV-

related genes

http://embomolmed.embopress.org/content/6/6/835.long


• CRISPR/CAS9 used to correct mutations in early human embryos.In April, Chinese scientists reported that they had used the CRISPR/CAS9 system to correct a mutation associated with -thalassemia in human embryos. These embryos had been fertilized with two sperm, and therefore had an extra set of chromosomes.

• 71 of 84 embryos survived mutatgenesis.

• 54 were genetically tested.• 28 were successfully spliced.• 4 contained the corrected

replacement DNA.

• CRISPR/CAS9 used to correct mutations in egg or sperm differentiated from primordial stem cells, which could then be used to make a “corrected” human embryo in vitro.


Using either embryonic stem cells or induced

pluripotent cells, researchers showed that they could make egg and

sperm precursors in a petri dish.

Use in vitro fertilization to make a “corrected”

human embryo.

CRISPR/CAS9

Differentiate egg/sperm

OvaScience, eGenesis actively working to develop this technique.

Is CRISPR/CAS9 safe to use for human gene therapy?

• Danger of “off-target” mutations.

– Getting the desired change made reliably– Getting ONLY the desired change

– Some scientists are more optimistic than others– It has a way to go– But they are working on it

Is CRISPR/CAS9 safe to use for human gene therapy?

• Danger of unknown genetic or epigenetic effects.– Some genes are known to have different effects during

development than they have in an adult organism.

– Some mutations have mixed effects • Sickle cell anemia carriers are less likely to die from

malaria.• A mutation that confers resistance to HIV also causes

elevated susceptibility to West Nile Virus.

What does the scientific community think?

“It cuts to the core of who we are as people, and it makes you ask if humans should be exercising that

kind of power.” --Jennifer Doudna, CRISPR pioneer

“People would look back at this moment in time and recognize it as a new chapter in ‘how humans control their bodies,’ [David Sinclair] said, because it would let parents determine ‘when and how they have children and how healthy those children are actually going to be.’”--David Sinclair, quoted in Technology Review. “An argument will be made that the

ultimate prevention is that the earlier you go, the better the prevention…I do think it’s the ultimate preventive, if we get to

the point where it’s very inexpensive, extremely safe, and very predictable…

[germline genome editing] is going to get to the point where it’s like you are doing

the equivalent of cosmetic surgery.”--George Church

“Many oppose germline modification on the grounds that permitting even unambiguously therapeutic interventions could start us down a path towards non-therapeutic genetic enhancement. We share

these concerns.”--Edward Lanphier

“Although scientists may be reluctant to debate ethics, we have a responsibility to do so and insights to offer. How would routine genome editing change our world? Would

we come to regard our children as manufactured products? Would marketers shape genetic fashions?

Would the “best” genomes go to the most privileged? If we cross this threshold, it's hard to see how we could ever

return.”Eric Lander

ETHICS OF HUMAN GERMLINE ENGINEERING—SOME THOUGHTS

Arguments Against• New territory: fundamental revision of human being, including future

generations• Violates equality of humans: Scientists performing editing are actors against

subjects/objects• It is impossible to obtain the informed consent of future generations whose

genomes will be altered.• It’s complicated: we don’t fully understand consequences of altering human

genes—and it may be impossible to predict in advance• Definitions of “disease” and “harm” are imprecise and inevitably involve social

biases. • Justice? Will availability and results be equitable?• “We don’t need it. We have alternatives—like PGD.” (!!)• Commodifies children and creates them as research subjects• Dignity of disabled people put at additional risk• Risk of “slippery slope” to enhancement/”designer kids”

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Arguments For• Some medical uses have no alternative (e.g., Huntington’s)• Biology of some applications (e.g., sickle cell) might be

circumscribed enough to be safe• Lure of the “ultimate preventative”• The human genome is not perfect or sacrosanct: we don’t accept

disease passively• Enhancing even a few people could greatly improve the prospects

for many or for all– And the enhanced would merit special respect/deference

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In reality, of course, if any one age really attains by eugenics and scientific education, the power to make its descendants what it pleases, all men who live after it are the patients of that power. They are weaker, not stronger: for though we may have put wonderful machines in their hands we have preordained who they are to use them.

C.S. Lewis Abolition of Man

Christian perspective?• Debates about genetic engineering, broadly, and

human germline modification specifically, expose fundamental philosophical differences among us about what it means to be human and the very purpose of scientific discovery.

• How can this technology be used to promote human dignity and human flourishing, consistent with God’s revealed will?

• What parameters need to be set to ensure that the technology serves the common good?

• Notable that several scientists and bioethicists who are supportive of other technologies that destroy human embryos nonetheless draw the line at human germline modification (Eric Lander, Ruth Malkin, Edward Lanphier).

• The technology is likely to overcome short term safety hurdles before we know the range of impacts of mutating (or “correcting”) a particular location in the human genome.

• The strong potential exists for significant harms to vulnerable populations.

• The considerations of justice and human dignity strongly favor banning human germline modification.

And…

• What is the animating idea behind gene editing?

• How would it take on a life of its own?

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Public opinion?

Current U.S. policy• No legislative ban.

• Congressional prohibitions on federal funding apply.• Dickey-Wicker appropriations amendment prohibits

federal funds from being used for research that “harms or destroys” human embryos.

• Guidelines in place since 2000 state that the NIH Recombinant DNA Advisory Committee “will not at present entertain proposals for germ line alteration.”

Current U.S. policy• FDA ruled in 1998 that human embryos are “Human

Cells, Tissues, and Cellular and Tissue-Based Products” (or HCT/Ps) that fall under its jurisdiction. As long as embryos are “minimally manipulated” or used for reproductive purposes, associated techniques and procedures do not require an IND (or clinical trials).

• Gene therapy IS regulated by FDA. Research into any genetic treatment designed to be used on human subjects requires an IND and extensive clinical trials.

Therapeutic or clinical applications of human germline genetic engineering would clearly fall under the jurisdiction of FDA. Currently, safety concerns alone would prohibit the development of gene therapies that involve germline modification.

Current U.S. policy• Ovascience is marketing the injection of mitochondria from

donor egg stem cells into a patient’s eggs which are then fertilized and implanted into her uterus. The procedure, called AUGMENT, is not available in the U.S. because the FDA is treating the procedure as a drug.

– According to the FDA, “FDA has jurisdiction over the use of human cells that have received transferred genetic material by means other than the union of gamete nuclei.”

• The jurisdictional reach of FDA into privately funded research on genetic modification of human embryos is ambiguous. Purely “scientific” research may not subject to regulation by FDA if treatment is never intended.

“The Public Health Service Act and the Federal Food, Drug, and Cosmetic Act give the FDA the authority to regulate cell and gene therapy products as biological products and/or drugs, which would include oversight of human germline modification. During development, biological products may be used in humans only if an investigational new drug application (IND) is in effect.”

Francis Collins, Director of NIH, in his 2015 statement on human germline genetic modification.

White House Statement, 2015

“The Administration believes that altering the

human germline for clinical purposes is a line that

should not be crossed at this time.”

NIH statement, 2015“NIH will not fund any use of gene-editing technologies in

human embryos. The concept of altering the human

germline in embryos for clinical purposes has been debated over many years

from many different perspectives, and has been viewed almost universally as

a line that should not be

crossed.”

“I am not in favor of the NIH policy and I believe that the Chinese paper shows a responsible way to move forward,” David Baltimore told Nature News.

Self-policing by the scientific community?

• Several influential scientists have called for a voluntary moratorium on research that involves human germline modification.

• CRISPR pioneer Jennifer Doudna organized a meeting of CRISPR researchers and bioethicists to discuss the application of CRISPR to human germline modification. 18 authors, including David Baltimore, Paul Berg, Alta Charo, George Church, George Daley, Jennifer Doudna, Ed Penhoet, Keith Yamamoto, published an editorial in Science entitled A Prudent Path Forward for Genomic Engineering and Germline Gene Modification, which called for a temporary “pause” while ethical, social, legal implications are discussed.

“Nessan Bermingham is CEO of Intellia Therapeutics, a Boston startup that raised $15 million last year to develop CRISPR into gene therapy treatments for adults or children. He says germ-line engineering ‘is not on our commercial radar,’ and he suggests that his company could use its patents to prevent anyone from commercializing it.” Technology Review.

• In the fall, the National Academy of Science and the National Academy of Medicine are convening a meeting to discuss ethical and policy implications of human germline modification.

“People feel “Science” (the field, not the magazine) promised that we would not try human

germline modification. That was, of course, an easy promise to make when it was impossible, like

promising not to try human reproductive cloning when it seemed impossible. And like the cloning promise,

which at the time, around 2000, seemed to help smooth the way for human non-reproductive

cloning/somatic cell nuclear transfer, swearing off germline modification made non-germline modification

more acceptable.”--Hank Greely, Stanford bioethicist, present at Napa

meeting convened by Doudna

• A voluntary, self-imposed moratorium is helpful in the short-term, but can not be a lasting solution.

Unlike physicians, whose licenses are granted by states, scientists do not have a formal mechanism regulating their activity. The federal government shapes the contours of biomedical inquiry on the basis of funding decisions, and institutional IRBs protect human subjects (not embryos). But no regulatory agency has clear jurisdiction over the work of privately funded scientists that are not developing human therapies (or working on potential biohazards).

Path forward?

• U.S. legislative ban on human germline genetic modification?

• Continued oversight by FDA. Better elaboration of FDA jurisdiction over human embryos?

• Lessons learned from stem cell/cloning debate: act prudentially BEFORE clamor for medical treatment overwhelms sober reflection of how to best use genome editing technology to advance human dignity and human flourishing.

Some summary points• As a society—nationally or globally, we have yet to develop a

suitable framework for evaluating emerging technologies that directly impact the future of our species.

• Christians should examine the ways we have been complicit in cultural lies that blur bioethical lines: – commodification of children– attitudes towards suffering and death– scientism.

• Challenge of developing more robust view of Christian citizenship. What kinds of issues concern your community? Can’t “outsource” public engagement on bioethics issues and public policy.

• Don’t trust the experts or think you know more than them—invite and expect them to engage the public respectfully and constructively

Q+A

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Bioethics: Some Cases in Point WV Wednesday

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