Editing Humanity?

The legal framework of genome

editing research in embryos
Anne Rotteveel - October 18th
In het nieuws
 Introduction

State of the art Research

Possibilities

Content Research Question

Methods of Research

State of the art Legal Framework

Findings & Discussion

Introduction
- We all know Gattaca
- What is actually
the state of the art?

Not only the question of

HOW to conduct research
in an ethical way

Also HOW FAR can or should we go?

What is the role of the legal framework?

Possibilities with embryos
- 1978: IVF (in vitro fertilisation)
- 1995: PGD (preimplantation genetic diagnostics: embryo selection)
- 2015: CRISPR/Cas9 (gene editing)
- 2017: IVG (in vitro gametogenesis) - only in mice
 What is the current legal framework for

research in embryonic gene modification

Research question in the Netherlands?

And what ought there to be with

regards towards the future?

Method
- Local legal framework Netherlands
- European/International legal framework
- Scientists view
- Interplay law and ethics
- Findings & Discussion
Current Legal Framework Biomedical Research
❖ International
➢ Declaration of Helsinki (non-binding)
❖ European Union
➢ Clinical Trial Regulation EU no 536/2014 (enters into force October 2018)
➢ General Data Protection Regulation no 679/2016 (since May 2018)
❖ National
➢ EU-regulations
➢ WMO (legal basis for functioning of CCMO and METC’s)
➢ Other legislation on data protection, pharmaceutical, patients rights
➢ Self regulation
Legal framework Netherlands
- WMO

13.c It is prohibited to conduct gene therapy clinical trials which are intended to result in modifications
to the subject’s germ line and individual genetic identity.

- Embryowet

Research with embryos and gametes whereby embryos are created fall under the Embryo Act → CCMO

Protocols for scientific research with gametes which are leftover after an IVF of KI treatment do not
have to be reviewed under the scope of the WMO or Embryo Act.

Informed consent just required from donor.

Embryo Act: P3, Article 10 and P4, Article 16
Regulation concerning research with embryos outside the human body
Research with embryos outside the human body allowed with no goal of pregnancy when:
a. it is reasonably plausible that the research will lead to the establishment of new insights in the field of medical
science;
b. it is reasonably plausible that the determination referred to under ‘a’ can not take place by other forms or methods
of scientific research than research with the relevant embryos or by research of a less intervening nature;

Research with embryos outside the human body allowed with the goal of pregnancy when:
a. it is reasonably plausible that the research will lead to the establishment of new insights in research or treatment
methods aimed at bringing about pregnancy and the birth of a healthy child;
b. it is reasonably plausible that the determination referred to under a can not take place by other forms or methods
of scientific research than research with embryos that are intended to bring about a pregnancy, or by research of a
lesser nature;
c. it is reasonably plausible that the interest to be served with the research is in proportion to the objections and
risks for the future child and the woman.
Embryo Act: P6, Article 24: Prohibited procedures with germ cells and embryos
It is prohibited to:

a. to create an embryo specifically and to use specially created embryos for scientific research and other purposes
than the realization of a pregnancy;
b. [this part has not yet entered into force];
c. use reproductive cells and embryos other than those referred to in subparagraph b for purposes other than those
for which they may be made available under this Act;
d. use reproductive cells and embryos for purposes authorized under this Act without having been made available for
that purpose;
e. an embryo outside the human body to develop for more than fourteen days;
f. to carry out actions involving germ cells or embryos with a view to the birth of genetically identical human
individuals;
g. to deliberately modify the genetic material of the nucleus of human germ cell cells with which pregnancy will be
established;
h. use cells grown from an embryo for purposes other than those for which they may be made available on the
grounds of Article 8, first paragraph, under b or Article 9, first paragraph, under a.
Embryo Act: P6, Article 24: Prohibited procedures with germ cells and embryos
1. It is prohibited to perform actions with germ cells or embryos with the intention of being able to
choose the sex of a future child.
2. The prohibition, referred to in ‘1’, does not apply if scientifically justified medical insights
constitute the risk of a serious sex-linked hereditary condition in the child and the actions take
place to prevent it.
International regulations
De Miguel Beriain, I. (2017). Legal issues regarding gene editing at the beginning of life: An EU perspective.
Regenerative medicine, 12(6), 669-679.

“This paper provides a critical and in-depth analysis of the current legal framework on this topic in the EU context and at
the national level in the member states. It also offers an alternative interpretation of the regulation, so as to help
researchers, practitioners, policy makers and society as a whole to find efficient responses to challenges that cannot wait
for a legally updated answer. As a final result, this paper will show that eugenic uses of CRISP–Cas and any kind of
modification intended to alter the human germ line are generally banned in the EU context, while basic research on
human embryos is mostly permitted. The legal status of therapeutic applications of CRISPR–Cas on early fetuses,
however, has not been adequately addressed by the EU zone regulation.”
International regulations
Ormond, K. E., Mortlock, D. P., Scholes, D. T., Bombard, Y., Brody, L. C., Faucett, W. A., ... & Musunuru, K. (2017).
Human germline genome editing. The American Journal of Human Genetics, 101(2), 167-176.

Ishii, T. (2017). Germ line genome editing in clinics: the approaches, objectives and global society. Briefings in
functional genomics, 16(1), 46-56.

Araki, M., & Ishii, T. (2014). International regulatory landscape and integration of corrective genome editing into in
vitro fertilization. Reproductive biology and endocrinology, 12(1), 108.

“Out of 39, 29 countries were found to ban germline gene modification. The remaining 10 countries include 9 countries
which were ambiguous about the legal status of the modification.”
Scientits
Law & Ethics
Charo, R. Alta. “The Legal and Regulatory Context for Human Gene Editing.” Issues in Science and Technology 32, no. 3
(Spring 2016).

“...I need to note that we are talking not only about government when we talk about law, regulation, and biotechnology.
We are really talking essentially about an ecosystem that is made up of government, the public, and private industry,
which produces innovative products based on the basic science and applied research coming out of our universities. The
ecology of this system is one in which there are many legal or policy issues that combine to affect whether biotechnology
is promoted or hindered in any particular country.”

van Beers, B. C. (2018). Van individu naar dividu: Lessen uit de Silicon Valley voor de regulering van kunstmatige
voortplanting. Tijdschrift voor Gezondheidsrecht, 42(3), 204-217.

van Beers, B. C. (2017). Imagining future people in biomedical law: From technological utopias to legal dystopias within
the regulation of human genetic modification technologies. In M. Ambrus, R. Rayfuse, & W. Werner (Eds.), Risk and the
regulation of uncertainty in international law (pp. 117-140). Oxford: Oxford University Press.

Kohn, D. B., Porteus, M. H., & Scharenberg, A. M. (2016). Ethical and regulatory aspects of genome editing. Blood,
blood-2016.
Law & Ethics
van Dijke, I., Bosch, L., Bredenoord, A. L., Cornel, M., Repping, S., & Hendriks, S. (2018). The ethics of clinical
applications of germline genome modification: a systematic review of reasons. Human Reproduction, 33(9), 1777-1796.

“GGM is still unsafe and insufficiently effective for clinical purposes. However, the progress made using Clustered
Regularly Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated system (Cas) has led scientists to expect
to overcome the technical hurdles in the foreseeable future. This has invited a debate on the socio-ethical and legal
implications and acceptability of clinical applications of GGM. However, an overview of the reasons presented in this
debate is missing. This article identified a total of 169 reasons, including 90 reasons for and 79 reasons against future
clinical application of GGM.”

CEG (2017). Geslachtscellen uit het lab: een ethische verkenning van IVG als nieuwe voortplantingstechniek.
Science or science fiction?
Janssens, A. C. J. (2016). Designing babies through gene editing: science or science fiction?. Genetics in Medicine, 18(12),
1186.

“Gene editing for favorable traits is not just a matter of tweaking the genes in the right direction. What makes people
intelligent, for instance, isn’t a combination of the “right genes” and the “right environment,” but the “right combination”
of genes and environment. Since the future environment of the embryo is unknown at the moment of editing, it will be
impossible to know what the right genes need to be.”

“Despite the successes in gene discovery of the past 10 years, our knowledge of the combined contribution of all genetic
variants is too limited for embryo editing. Even when all genes and their complex interactions are completely
understood, our ability to use gene editing for favorable traits will remain limited because human traits are just not
genetic enough.”

“This is why the traits people might want to enhance can’t be programmed in the embryo, not even with the most
accurate and reliable version of CRISPR. The technology is not the limitation for enhancing babies – nature is.”
Where to draw the line?
Findings / discussion
❖ In the Netherlands not yet allowed
❖ International regulation (not necessarily law) should be negotiated
❖ Especially including countries such as US, India and China
❖ Interplay between law and ethics is important
 What is the current legal framework for

research in embryonic gene modification

Research question in the Netherlands?

And what ought there to be with

regards towards the future?

Questions?