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Ethical Reflections on the Conditions Surrounding the First Genome-Edited Babies [Version 2; Peer Review: 2 Approved] Wellcome Open Research 2021, 5:216 Last updated: 04 AUG 2021 OPEN LETTER Making sense of it all: Ethical reflections on the conditions surrounding the first genome-edited babies [version 2; peer review: 2 approved] Qi Chen1, Yonghui Ma 1, Markus Labude2, G Owen Schaefer2, Vicki Xafis 2, Peter Mills 3 1Centre for Bioethics, Medical School, Xiamen University, Xiamen, 361102, China 2Centre for Biomedical Ethics, National University of Singapore, Singapore, 117597, Singapore 3Nuffield Council on Bioethics, London, WC1B 3JS, UK v2 First published: 16 Sep 2020, 5:216 Open Peer Review https://doi.org/10.12688/wellcomeopenres.16295.1 Latest published: 23 Jun 2021, 5:216 https://doi.org/10.12688/wellcomeopenres.16295.2 Reviewer Status Invited Reviewers Abstract In November 2018 the birth of the first genome-edited human beings 1 2 was announced by Chinese scientist, He Jiankui. The ensuing ethical controversy, institutional investigations and legal proceedings led to version 2 the revision of standards, rules and procedures at many levels. (revision) report report Arguably, however, these developments have not fundamentally 23 Jun 2021 changed the conditions or the culture that nourished He Jiankui’s vaulting ambition in the first place and enabled it to find expression. version 1 In this paper we explore the clinical, regulatory and societal 16 Sep 2020 report report circumstances of the ‘gene-edited baby’ case, the political, cultural and economic conditions that created a radical and dangerous climate for biotechnology innovation, and the responsibilities of the international 1. Giulia Cavaliere , King's College London, research community, many of whose members were apprised of Dr London, UK He’s intentions. The aim is not to heap anathemas on the heads of implicated individuals but to draw attention to the need for different 2. Song Lingqiao, McGill University, Montreal, communities (researchers, authorities and domestic publics) to play a Canada part actively in the governance of biomedical innovation and for research to be bridled by human values. Yann Joly , McGill University, Montreal, Keywords Canada He Jiankui, Human germline genome editing, CRISPR-Cas9, HIV, Gene Any reports and responses or comments on the editing, Twins/genetics, Research ethics, Research governance article can be found at the end of the article. This article is included in the GFBR: Genome editing for human benefit: ethics, engagement and governance collection. Page 1 of 20 Wellcome Open Research 2021, 5:216 Last updated: 04 AUG 2021 Corresponding author: Peter Mills ([email protected]) Author roles: Chen Q: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Ma Y: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Labude M: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Schaefer GO: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Xafis V: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Mills P: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests: No competing interests were disclosed. Grant information: This work was supported by the Wellcome Trust through funding to the Global Forum on Bioethics in Research (GFBR). GFBR funding is provided by The Wellcome Trust, the Bill & Melinda Gates Foundation [OPP1151904], the National Institutes of Health and the UK Medical Research Council. Additionally, YM received funding from the President's Foundation project 2019 of Xiamen University on ‘Ethical and governance considerations in human genome editing’. This work was also supported by the Singapore Ministry of Health’s National Medical Research Council under its NMRC Funding Initiative grant (NMRC/CBME/2016) in relation to the involvement of OS, VX, and ML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2021 Chen Q et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Chen Q, Ma Y, Labude M et al. Making sense of it all: Ethical reflections on the conditions surrounding the first genome-edited babies [version 2; peer review: 2 approved] Wellcome Open Research 2021, 5:216 https://doi.org/10.12688/wellcomeopenres.16295.2 First published: 16 Sep 2020, 5:216 https://doi.org/10.12688/wellcomeopenres.16295.1 Page 2 of 20 Wellcome Open Research 2021, 5:216 Last updated: 04 AUG 2021 preferences; the perceived policy vacuum in the wake of REVISED Amendments from Version 1 technological developments in genome editing (in particular the rapid elaboration and diffusion of CRISPR-Cas9 tech- This version responds to the helpful comments of reviewers on the initial version. In particular: the aims of the paper are niques) and the significance of public opinion in this context; clarified; material in the section on ‘Clinical, regulatory and the complex motivations and incentives that bear upon ambitious societal conditions’ is clarified; legal information is added to biotechnology entrepreneurialism in contemporary China and the section on ‘Political, cultural and economic conditions’; elsewhere; the integrity, role and responsibilities of scientists clarifications have been made to improve the balance of the section on ‘silence and complicity’; editorial improvements and the international scientific community; the traction of global have been made and additional references have been supplied bioethical norms and missteps in cross-cultural understanding; throughout. Additionally, minor amendments have been and wider questions for society about the role of biomedical made to the order in which the authors are listed and the technologies in the collective response to societal challenges, acknowledgements. such as the prevalence of HIV and genetic disease. In reflecting Any further responses from the reviewers can be found at on the – so far as we know – singular case of Dr He and his the end of the article collaborators our interest is not forensic but normative: our aims are to begin to understand whether this case, though singular, should truly be seen as exceptional, to what extent the conditions that appear to have been conducive to Dr He’s Disclaimer interventions may still prevail, and what needs to change in the The views expressed in this article are those of the author(s). light of the incident if we should wish to forestall a recurrence. Publication in Wellcome Open Research does not imply Due to the broad range of issues considered, this paper cannot endorsement by Wellcome. provide the in-depth analysis these issues deserve; rather it is intended as a springboard for further analyses. Introduction The facts of the case, though they were initially met with incre- Clinical, regulatory and societal conditions dulity, are now more or less established: Dr He Jiankui, a Dr He originally announced the birth of genome edited twin biotechnology entrepreneur and researcher at the Southern girls on YouTube on 25 November 2018. Subsequently, at University of Science and Technology in Shenzhen, China, the Second International Summit on Human Genome Editing recruited a number of couples to a project that led to the birth, held in Hong Kong, he revealed that another woman was in in 2018, of the first babies from embryos that had their DNA the early stages of pregnancy with a genetically modified deliberately modified using the genome editing tool CRISPR- embryo. Dr He’s claims not only caused shock and controversy Cas91. The objective of these procedures was not connected in the scientific community and the wider society, but also with the avoidance of an imminent risk to the future children prompted urgent reflection on the application and regulation of but to confer to them the advantage of inherent resistance to emerging technologies in China and elsewhere4. The actions HIV, with which the male partner of each couple was infected. of Dr He and his associates posed numerous ethical challenges These treatments, described at the Second International Sum- not just to China but also to the wider world. At the same time, mit on Human Genome Editing in Hong Kong in November this event prompted the further development of ethical norms 2018, caused immediate consternation among scientists and governing genome editing and stimulated public discussion. We the public, provoked numerous statements of condemnation review this event from three aspects – clinical, regulatory and from scientific and ethical bodies, and led to a number of societal – before proceeding to discuss its wider implications academic, institutional and official investigations around the for Chinese and international research. world, including a court case that ended with the conviction of Dr He and two associates in December 2019 for illegally Clinical Research practising medicine2,3. Three important features of ethical medical research are that researchers should (1) seek the informed consent of their patients Of the many questions that the ‘gene-edited baby case’ before carrying out procedures, (2) fulfil a duty of care not provoked, among the most perplexing must be: given the to carry out procedures where the risks cannot be justified in already salient and near-universal opposition
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