Human germline gene editing. Recommendations of the European Society of Human Genetics and the European Society of Human Reproduction and Embryology.*

Abstract Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if GLGE would become safe and effective. What were the arguments behind this legislation, and are they still 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? The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. After consulting its membership and experts, this final version of the Recommendations was endorsed by the Executive Committee and the Board of the respective Societies in May 2017. Taking account of ethical arguments, we argue that both basic and pre-clinical research regarding human GLGE can be justified, with conditions. Furthermore, while clinical GLGE would be totally premature, it might become a responsible intervention in the future, but only after adequate pre-clinical research. Safety of the child and future generations is a major concern. Future discussions must also address priorities among reproductive and potential non-reproductive alternatives, such as PGD and somatic editing, if that would be safe and successful. The prohibition of human germline modification, however, needs renewed discussion among relevant stakeholders, including the general public and legislators.

Download Full-text

Responsible innovation in human germline gene editing. Background document to the recommendations of ESHG and ESHRE†‡

Human Reproduction Open ◽

10.1093/hropen/hox024 ◽

2018 ◽

Vol 2018 (1) ◽

Cited By ~ 3

Author(s):

Guido de Wert ◽

Björn Heindryckx ◽

Guido Pennings ◽

Angus Clarke ◽

Ursula Eichenlaub-Ritter ◽

...

Keyword(s):

European Society ◽

Gene Editing ◽

New Technologies ◽

Genetic Disorders ◽

Full Range ◽

Basic Research ◽

Clinical Applications ◽

Human Reproduction ◽

Responsible Innovation ◽

Germline Gene

Abstract Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, pre-clinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g. gene editing goes against nature) do not seem convincing while consequentialist objections (e.g. safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.

Download Full-text

Designing Preclinical Studies in Germline Gene Editing: Scientific and Ethical Aspects

Journal of Bioethical Inquiry ◽

10.1007/s11673-019-09947-9 ◽

2019 ◽

Vol 16 (4) ◽

pp. 559-570 ◽

Cited By ~ 1

Author(s):

Anders Nordgren

Keyword(s):

Clinical Trials ◽

Experimental Design ◽

Animal Studies ◽

Gene Editing ◽

Preclinical Studies ◽

Germline Gene ◽

Ethical Aspects ◽

Human Germline Gene Editing ◽

First Time ◽

Modest Level

AbstractHuman germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design (with exception of implantation). Only in this way can uncertainty about risk for harm (safety) and prospect of benefit (efficiency) in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated.

Download Full-text

The Demands of CRISPR’s World

Ethics & Medics ◽

10.5840/em20164146 ◽

2016 ◽

Vol 41 (4) ◽

pp. 1-2

Author(s):

J. Benjamin Hurlbut ◽

Keyword(s):

Human Rights ◽

Genetic Engineering ◽

Gene Editing ◽

Human Life ◽

European Countries ◽

Future Generations ◽

Genetic Enhancement ◽

Germline Gene ◽

Technical Possibility ◽

Human Germline Gene Editing

A growing chorus of voices is declaring that CRISPR will revolutionize the ability to control life, including human life. As genetically altering future generations becomes technically realistic, it raises the prospect of genetic enhancement and the specter of eugenics. Prominent scientists are calling for international guidelines to govern human applications of gene-editing technology. They argue that the technical possibility of human germline gene editing makes ethical deliberation urgent. Now that the technology is upon us, the time has come to ask whether we want it. Human germline genetic engineering has long been marked as a morally significant boundary, and in numerous countries it is explicitly prohibited by law. The Oviedo Convention, a legally binding treaty among twenty-nine European countries, prohibits it as a violation of human rights and dignity. Nevertheless, numerous commentators argue that prohibitions made before it was technically possible meant little, and past proscriptions must now be revised.

Download Full-text