A Consensus Study Report on Heritable Human Genome Editing

Tuesday, September 8, 2020

Rapidly advancing technical capabilities in genome editing, and the reported use of heritable human genome editing (HHGE) in 2018 leading to the birth of children whose DNA had been edited, led to renewed global calls for consideration of the scientific, societal, and governance issues associated with this technology. The possibility of heritable editing occurs when alterations to genomic DNA are made in gametes (eggs or sperm) or any cells that give rise to gametes, including the single cell zygote resulting from fertilization of an egg by a sperm cell, or cells of an early embryo. Changes made to the genetic material in such cells can be passed on to subsequent generations. No country has yet decided that it would be appropriate to move forward clinically with HHGE, and clinical use of the technology is currently explicitly prohibited or not explicitly regulated in many countries.

HHGE could represent an important option for prospective parents with a known risk of transmitting a genetic disease to have a genetically- related child without that disease and its associated morbidity and mortality. However, it will be essential to establish safe and effective methodologies that could form the necessary steps in a translational pathway for any clinical uses of HHGE. Assuming the existence of a safe and effective methodology, the decision to permit the clinical use of HHGE and, if so, for which specific applications, must ultimately rest with individual countries following informed societal debate of both ethical and scientific considerations.

This societal debate would include a range of issues and questions raised by HHGE, as well as how it might address important unmet needs within a country, informed by the views of patients and their families; ethical, moral, and religious views; potential long-term societal implications; and issues of cost and access. The societal considerations are the subject of ongoing national and international conversations, including current work by the World Health Organization’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, which is deliberating on national and global governance.

The International Commission on the Clinical Use of Human Germline Genome Editing, which was convened by the U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the U.K.’s Royal Society and includes members from 10 countries, was tasked with addressing the scientific considerations that would be needed to inform broader societal decision-making. This task involves considering technical, scientific, medical, and regulatory requirements, as well as those societal and ethical issues that are inextricably linked to these requirements, such as the significance of uncertainties related to outcomes, and potential benefits and harms to participants in clinical uses of HHGE.

This report does not make judgments about whether any clinical uses of a safe and effective HHGE methodology, if established by pre-clinical research, should at some point be permitted. The report instead seeks to determine whether the safety and efficacy of genome editing methodologies and associated assisted reproductive technologies are or could be sufficiently well developed to permit responsible clinical use of HHGE; identifies initial potential applications of HHGE for which a responsible clinical translational pathway can currently be defined; and delineates the necessary elements of such a translational pathway. It also elaborates national and international mechanisms necessary for appropriate scientific governance of HHGE, while recognizing that additional governance mechanisms may be needed to address societal considerations that lie beyond the Commission’s charge.