Bioethics for ‘dummies’:

Gene editing, NIPT

28 May 2017, ESHG, Copenhagen

Prof.dr. Martina Cornel, VU University Medical Center, Amsterdam

www.vumc.com/researchcommunitygenetics
Overview
• Domains
– Research ethics
– Clarify the debate
– Health care

• Principles
– Autonomy
– Individual vs. Collective

• NIPT

• Gene editing
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Ethics
• Do good

• Why, what do you mean, what values?

• In health care

• Is it allowed to…

• In research

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Ethics
• Not only answers

• Asking good questions

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(1) Research ethics
• Medical ethical committee
• Institutional Review Board

• Is is allowed to do this experiment in humans?

– Information on proposed intervention
– Drawing blood, taking sample
– Giving medication that is not the “standard treatment”
– Consent

• Declaration of Helsinki adopted in June 1964

• Not a law - effort of the medical community to regulate research
itself
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(2) Clarify the debate
• Bioethicist help to understand relationships among life
sciences, biotechnology, medicine, politics, law and philosophy.

• Why do we argue the way we argue.

• What values are behind controversial issues.

• For a decision to be made, what are the arguments in favor and

against.

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(3) In health care
• Ethical practice in profession-led health care.
• For physicians ethics is an element of professionalism.
• The CANMEDS competency “professionalism” encompasses
ethical practice

• The Hippocratic Oath

A fragment of the Oath on the 3rd-

century Papyrus Oxyrhynchus
2547.

Source: Wikipedia 7
In health care
• I will use treatment to help the sick according to my ability and
judgment, but never with a view to injury and wrong-doing.
– Beneficence
– Non-maleficence

• Respect the privacy

– “holding such things to be holy secrets”

• Recognise skills of yourself & colleagues (I know not..; refer)

– No surgery (centuries Before Christ)
– Qualified and competent (2017)

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Gene editing, NIPT
• Questions at the beginning of life
– gene editing
– non-invasive prenatal testing (NIPT)

• I will focus on the contributions of the Public and Professional

Policy Committee (PPPC) of ESHG

• Developed recommendations for responsible health care

practice and clarify debate
– As in second and third domains of ethics

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Overview
• Domains

• Principles
– Autonomy
– Individual vs. Collective

• NIPT

• Gene editing

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Principles?
• To clarify why we argue the way we argue, we need to look
beyond the surface: what are the principles?

• For human genetic research, these have been well developed

by Knoppers & Chadwick:

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Principles?
• autonomy, • reciprocity,
• privacy, • mutuality,
• justice, • solidarity,
• quality and • citizenry and
• equity • universality

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Genetic counseling (Am J Hum Genet 1975;27:240-2)

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Autonomy
• Patient or participant chooses
• Patient or participant can say no

At the beginning of life difficult choices to make, where people /

cultures / populations / religious groups decide different
– Choose (not) to have children

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Autonomy
• Patient or participant chooses
• Patient or participant can say no
Eliminating tinder for Tay-Sachs
http://www.sajr.co.za/news-and-articles/2014/12/29/eliminating-
tinder-for-tay-sachs-18-others

At the beginning of life difficult choices to make, where people /

cultures / populations / religious groups decide different
– Choose (not) to have children
– Different partner
– Prenatal testing and abortion if affected
– Avoid risk by using donor sperm (and not become biological
parent)

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Autonomy vs. coercion
First half of previous century in many countries
• Some people isolated from "normal" society
• Segregation
• Compulsory sterilization of "feeble-minded"

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Autonomy in health care

• If the physician proposed a treatment or test or intervention

– You can say “no”

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Autonomy in health care vs. research

• If the physician proposed a treatment or test or intervention

– You can say “no”
• Also in research: I agree to participate (or not)

NOTE:
• Individual autonomy
• In genetics the patient often is the family
• E.g. a couple decides on their pregnancy

• Also in research values related to collective level

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Principles?
• autonomy, • reciprocity,
• privacy, • mutuality,
• justice, • solidarity,
• quality and • citizenry and
• equity • universality

collective

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Individual vs. group
• I participate in research in the interest of “patients like me”
• Vs. there is a small chance that I profit
• My genome will provide information about people with same
ancestry

• In children:
– Reluctance to include in research: avoid harm
– But for some childhood disorders one would never be able to
further develop therapy

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Overview
• Domains

• Principles
– Autonomy
– Individual vs. Collective

• NIPT

• Gene editing

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Non-invasive prenatal testing (NIPT)
• From DNA in maternal plasma ~10% is from foetal (placental)
origin;
• RhD+ DNA in blood of RhD- mother, must be foetal!

Man RhD+

Woman RhD+

BMJ 2011: trisomie 21

Woman RhD-
PLoS One 2011: ook tris
13&18
NIPT for aneuploidy testing
• In many countries screening during pregnancy for Down syndrome
and other aneuploidies
• If anomaly detected, options are to terminate the pregnancy or not

• Now 5-7% referrals after combined testing; invasive chorionic villi

or amniocentesis needed for diagnostic test

• NIPT offers improved accuracy – less invasive testing – higher

sensitivity and specificity (but still confirmation needed)

• should not lead to lower standards for pretest information and

counseling
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NIPT recommendations
EJHG (2015) 23, 1438–1450

• It has the potential of helping the practice better achieve its aim
of facilitating autonomous reproductive choices.
• To evaluate this aim, it is not sufficient to report on the number
of participants, the uptake or the prevalence of aneuploidies.
– Include measure of informed decision making
• Crucial elements for the health care system include information
and counseling, education of professionals, accountability to all
stakeholders including children born from screened
pregnancies and persons living with the conditions targeted in
prenatal screening and promotion of equity of access.

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NIPT for all?
• Ethical principles are often connected

• Equity?

• If women are to make an autonomous choice, this can only be

achieved if all women have access (and could pay for it),

• And if, whatever their choice, they and their children will be
taken care of.
– Decline or accept test
– Terminate pregnancy or not

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Overview
• Domains

• Principles
– Autonomy
– Individual vs. Collective

• NIPT

• Gene editing

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Gene editing - somatic
• “beneficence” (doing good) vs.
“maleficence” (doing harm):
– how safe is it?
• If safe and effective – change gene in
stemcells and give them back to patient
lacking enzyme/function (somatic gene
editing)
• In terms of ethics – simple case?

Araki et al
Trends in Biotechnology, 2016, Vol. 34, No. 2
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Germline gene editing?
• The Council of Europe Committee on bioethics DH-BIO
stressed the Oviedo Convention as the only international
legally binding treaty addressing human rights in the biomedical
field.
The article 13 in the convention limits the purposes of any
intervention on the human genome, including in the field of
research, to prevention, diagnosis or therapy.
In addition, it prohibits any gene modification of embryos that
would be passed on to future generations

Source: http://www.coe.int/en/web/bioethics/-/gene-editing
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Germline gene editing?
Clinical trials regulation Art 90:

No gene therapy clinical trials may be carried out which result in

modifications to the subject's germ line genetic identity.

REGULATION (EU) No 536/2014 OF THE EUROPEAN

PARLIAMENT AND OF THE COUNCIL of 16 April 2014 on
clinical trials on medicinal products for human use, and repealing
Directive 2001/20/EC

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PPPC doc Germline Gene Editing
• The PPPC of ESHG collaborates with The European Society of
Human Reproduction and Embryology (ESHRE).
• Together developing recommendations especially for
reproductive gene editing.
• What were the arguments behind this legislation, and do these
still apply and are they still considered convincing?
• If a technique can help to avoid serious genetic disorders, in a
safe and effective way, would this be a reason to reconsider
earlier standpoints?

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PPPC doc Germline Gene Editing
• Categorical objections

– NO by principle (not natural, against human dignity)

• Consequentialist objections

– NO because of the consequences

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PPPC doc Germline Gene Editing
• Categorical objections to Germline Gene Editing - in terms of
being at odds with e.g. naturalness, human dignity, or the
preservation of the human gene pool as a common heritage –
are often used both in public debate and legal discourse.

• While these objections may be relevant for possible (mostly

rather theoretical) enhancement-like applications of Germline
Gene Editing , they seem unconvincing when it comes to
possible applications of Germline Gene Editing with a clear
therapeutic or preventive aim.

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PPPC doc Germline Gene Editing
• No convincing arguments for “never edit the germline” for
serious condition
– we need better understanding of these categorical arguments
to inform the debate

• Safety (this child and future generations)

• Other ways to avoid serious condition? (preimplantation genetic

diagnosis, prenatal diagnosis & termination of pregnancy)
Would the number of cases be (too) small?
– Both parents CF e.g.
– Or: PGD and few embryos when 2 traits involved (Hb and
HLA) 33
PPPC doc Germline Gene Editing
• Only after establishing a more robust knowledge acquired from
basic research, might possible future clinical applications be
considered which would require further societal and
professional discussions. Both for scientific and moral reasons,
as a precondition for any potential clinical applications of GLGE,
adequate preclinical GLGE is necessary.

• The use of research embryos could be morally justified, subject

to ethical, legal and societal oversight.

• More scrutiny and debate needed on potential consequences

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Conclusions
• Ethics for questions and answers

• Principles: autonomy, equity, individual/collective

• For NIPT autonomy → information, evaluation

• For Germline Gene Editing: categorical objections do not seem

convincing. Debate needed.

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