International Reporting Mechanism for Unethical Germline Gene Editing Experiments Is Needed

Abstract

Recent reporting found that a number of scientists internationally knew about the experiment resulting in the birth of the first gene-edited babies well before the news broke. Because scientists have a responsibility to reveal such activities, an international governance mechanism for reporting unethical gene editing experiments should be established. Recent reporting found that a number of scientists internationally knew about the experiment resulting in the birth of the first gene-edited babies well before the news broke. Because scientists have a responsibility to reveal such activities, an international governance mechanism for reporting unethical gene editing experiments should be established. The 2018 revelation of the birth of the first babies whose DNA had been edited shocked the world and was met almost instantly with condemnation from scientists, ethicists, and policymakers around the world [1.Cyranoski D. Ledford H. Genome-edited baby claim provokes international outcry.Nature. 2018; 563: 607-608Crossref PubMed Scopus (115) Google Scholar] (Box 1). The news was not a shock to quite everyone, however. A recent article reveals that a large number of individuals around the world knew about the experiment, in one form or another, before the news broke internationally [2.Cohen J. The untold story of the ‘circle of trust’ behind the world’s first gene-edited babies.Science. 2019; (Published online August 1, 2019. https://www.sciencemag.org/news/2019/08/untold-story-circle-trust-behind-world-s-first-gene-edited-babies)Google Scholar]. He Jiankui, who led the experiment, had built up an international network of collaborators for several of his biotechnology ventures and at various stages communicated progress of his experiment to international colleagues. Some now say they tried to discourage him, but none made known the ongoing experiment to the broader international community.Box 1An Unethical ExperimentIn 2018, the news broke that the first babies whose DNA had been edited as embryos were born. The goal of the experiment was to confer the babies with immunity to HIV by disabling the CCR5 gene [1.Cyranoski D. Ledford H. Genome-edited baby claim provokes international outcry.Nature. 2018; 563: 607-608Crossref PubMed Scopus (115) Google Scholar].Numerous ethical failings of the experiment have been pointed out: the germline gene editing science was premature, making the technique too risky for clinical application; there was a lack of medical necessity because the edit would not prevent a devastating heritable disorder but rather would confer immunity to HIV transmission; informed consent was questionable, with consent forms referring to the trial as a ‘vaccine study’; and oversight was limited, with the institutions involved later claiming ignorance of the trial [13.Greely H.T. CRISPR’d babies: human germline genome editing in the ‘He Jiankui affair’.J. Law Biosci. 2019; 6: 111-183Crossref PubMed Scopus (43) Google Scholar].Authorities in China, where the experiment occurred, subsequently shut down the study, and the scientist who conducted the experiment, He Jiankui, was fired from his university and sentenced to three years in prison for ‘illegal medical practices’ [14.Normile D. Chinese scientist who produced genetically altered babies sentenced to 3 years in jail.Science. 2019; (Published online December 30, 2019. https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail)Crossref Google Scholar]. In 2018, the news broke that the first babies whose DNA had been edited as embryos were born. The goal of the experiment was to confer the babies with immunity to HIV by disabling the CCR5 gene [1.Cyranoski D. Ledford H. Genome-edited baby claim provokes international outcry.Nature. 2018; 563: 607-608Crossref PubMed Scopus (115) Google Scholar]. Numerous ethical failings of the experiment have been pointed out: the germline gene editing science was premature, making the technique too risky for clinical application; there was a lack of medical necessity because the edit would not prevent a devastating heritable disorder but rather would confer immunity to HIV transmission; informed consent was questionable, with consent forms referring to the trial as a ‘vaccine study’; and oversight was limited, with the institutions involved later claiming ignorance of the trial [13.Greely H.T. CRISPR’d babies: human germline genome editing in the ‘He Jiankui affair’.J. Law Biosci. 2019; 6: 111-183Crossref PubMed Scopus (43) Google Scholar]. Authorities in China, where the experiment occurred, subsequently shut down the study, and the scientist who conducted the experiment, He Jiankui, was fired from his university and sentenced to three years in prison for ‘illegal medical practices’ [14.Normile D. Chinese scientist who produced genetically altered babies sentenced to 3 years in jail.Science. 2019; (Published online December 30, 2019. https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail)Crossref Google Scholar]. In this article, we argue that revealing such activities is in line with scientists’ responsibilities to uphold the integrity and trustworthiness of the scientific enterprise. However, the international context complicates the situation; it is not clear whom individuals who knew about the experiment should have approached. To fill this gap, we suggest that, in line with recent proposals [3.National Academy of Medicine, National Academy of Sciences, and the Royal Society Heritable Human Genome Editing. National Academies Press, 2020Google Scholar], an international mechanism for reporting unethical germline gene editing experiments should be established. The World Health Organization (WHO) would be well placed to take the lead, given its substantial international influence, and the reporting mechanism could be attached to the WHO’s recently established International Clinical Trials Registry Platform (Box 2).Box 2Potential WHO Reporting MechanismThe WHO’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing has already established an International Clinical Trials Registry Platform on gene editing clinical trials [15.Chaib F. WHO launches global registry on human genome editing [news release].Publisher Name: World Health Organizationhttps://www.who.int/news-room/detail/29-08-2019-who-launches-global-registry-on-human-genome-editingDate: 2019Google Scholar]. A mechanism to inform the WHO of clinical trials and other clinical studies that have failed to register on that platform could be established, with the aim of ensuring the registry is complete and the international community is well apprised of the gene editing trials happening around the world. This mechanism would require some degree of support from governments and international bodies, both for funding and for providing the relevant expertise.A successful mechanism would need to accomplish at least two things. First, the mechanism must minimize, to the extent practical, the risk of retaliation against those making reports. Because of the mechanism’s international nature, it will have limited ability to protect those making reports once they are identified; therefore, the identity of those making reports should be kept in strictest confidence. Second, the mechanism must make efforts to verify reports made, to avoid spurious and unfounded accusations. Although the mechanism would be unable to compel the provision of evidence, it could take on the approach of investigatory journalists: conducting interviews and reviewing documentary evidence provided by those making reports. The WHO’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing has already established an International Clinical Trials Registry Platform on gene editing clinical trials [15.Chaib F. WHO launches global registry on human genome editing [news release].Publisher Name: World Health Organizationhttps://www.who.int/news-room/detail/29-08-2019-who-launches-global-registry-on-human-genome-editingDate: 2019Google Scholar]. A mechanism to inform the WHO of clinical trials and other clinical studies that have failed to register on that platform could be established, with the aim of ensuring the registry is complete and the international community is well apprised of the gene editing trials happening around the world. This mechanism would require some degree of support from governments and international bodies, both for funding and for providing the relevant expertise. A successful mechanism would need to accomplish at least two things. First, the mechanism must minimize, to the extent practical, the risk of retaliation against those making reports. Because of the mechanism’s international nature, it will have limited ability to protect those making reports once they are identified; therefore, the identity of those making reports should be kept in strictest confidence. Second, the mechanism must make efforts to verify reports made, to avoid spurious and unfounded accusations. Although the mechanism would be unable to compel the provision of evidence, it could take on the approach of investigatory journalists: conducting interviews and reviewing documentary evidence provided by those making reports. When He Jiankui’s experiment proceeded outside the glare of the public eye, it appeared to face few impediments. Initial news coverage claimed that the experiment received approval from a local ethics panel (https://apnews.com/4997bb7aa36c45449b488e19ac83e86d), and He was evidently able to obtain funding to conduct the experiment. (https://www.statnews.com/2019/02/25/crispr-babies-study-china-government-funding/). As noted in Box 1, Chinese authorities ordered the study to shut down only after the story broke, at which time the first births had already occurred – a pair of twins. According to a Chinese court, another pregnancy of a baby whose DNA was edited by He Jiankui prior to the study shutdown resulted in a live birth [4.Cyranoski D. What CRISPR-baby prison sentences mean for research.Nature. 2020; 577: 154-155Crossref PubMed Scopus (11) Google Scholar]. Had there been broad international knowledge of the experiment at an earlier stage, this could have had the salutary effect of getting it shut down sooner. If the research plans had been made known when the experiment was still in the planning stage, the initial births might have been prevented entirely. Even an announcement after the twins were born might have prevented the second pregnancy. Stopping the study early would have, first and foremost, spared the mothers involved from being subjected to irresponsible, invasive, and burdensome research. It also would have avoided the risky outcomes for the twins who were born. In at least one twin, the edit was only partly successful [5.Wang H. Yang H. Gene-edited babies: what went wrong and what could go wrong.PLoS Biol. 2019; 17e3000224Crossref PubMed Scopus (20) Google Scholar], and the long-term effects of the imperfect procedure remain unknown. More broadly, earlier reporting could have upheld the trustworthiness of the international scientific community to self-regulate and recognize its social, professional, and ethical responsibilities. Because He Jiankui’s experiment was conducted against international expectations and without prior public discussion, it meant that individuals around the world were denied the opportunity to deliberate and openly discuss the merits of such an intervention [6.Committee on Science, Technology, and Law; Policy and Global Affairs; National Academies of Sciences, Engineering, and Medicine Olson S. International Summit on Human Gene Editing: A Global Discussion. National Academies Press (USA), Washington (DC)2016Google Scholar]. To ground the responsibility to report, we should look to well-recognized professional codes of conduct. These align with standards that scientists themselves consider important and have been codeveloped by the scientific community, ethicists, policymakers, and other stakeholders. They set a higher bar than general duties the lay public may have because scientists rely on the integrity and trustworthiness of the profession in order for their work to be accepted, supported, and integrated into practice. A responsibility to report unethical research is reflected in a number of reputable national and international research codes of conduct [7.UK Research Integrity Office Code of Practice for Research: Promoting Good Practice and Preventing Misconduct. Aldridge Press, 2009Google Scholar,8.Resnik D.B. Shamoo A.E. The Singapore statement on research integrity.Account. Res. 2011; 18: 71-75Crossref PubMed Scopus (49) Google Scholar] (https://www.who.int/docs/default-source/documents/ethics/code-of-conduct-for-misconduct-in-research-pamphlet-en.pdf). Although these codes have traditionally been applied to cases of fraud, plagiarism, or similar instances, the basis of the responsibility to report dishonest behavior is broader: ‘undermin[ing] the trustworthiness of research’ [8.Resnik D.B. Shamoo A.E. The Singapore statement on research integrity.Account. Res. 2011; 18: 71-75Crossref PubMed Scopus (49) Google Scholar]. Editing the germline in an experiment that involves unjustifiably high risks and questionable benefits, that exploits vulnerabilities, and that involves inadequate consent would rightly lead members of the public to view researchers as less than trustworthy to look after the interests of participants as well as the general public in the course of their research. In the current context, unethical germline gene editing experiments would likely undermine the trustworthiness of research, for the reasons enumerated above: Germline gene editing is widely considered by the international scientific community as inappropriate for current clinical research. In addition, there is also general recognition that we should only proceed with clinical research applications after a period of robust discussion and dialogue where novel and contested applications of new technologies are concerned [3.National Academy of Medicine, National Academy of Sciences, and the Royal Society Heritable Human Genome Editing. National Academies Press, 2020Google Scholar,6.Committee on Science, Technology, and Law; Policy and Global Affairs; National Academies of Sciences, Engineering, and Medicine Olson S. International Summit on Human Gene Editing: A Global Discussion. National Academies Press (USA), Washington (DC)2016Google Scholar,9.Lander E.S. et al.Adopt a moratorium on heritable genome editing.Nature. 2019; 567: 165-168Crossref PubMed Scopus (155) Google Scholar]. Deviations from these norms would rightly undermine the public’s ability to trust scientists to conduct research in an ethical, socially licensed manner. As such, the professional responsibility to report would apply to current clinical research applications of germline gene editing. This is especially important in the context of germline gene editing because the United Nations Educational, Scientific and Cultural Organization (UNESCO) has recognized the genome as the common heritage of humankind [10.United Nations Educational, Scientific and Cultural Organization (UNESCO) Universal Declaration on the Human Genome and Human Rights.1997Google Scholar]. Whether and how to alter the human germline is then a matter of global significance, and reporting experiments would help promote international dialogue on the merits of conducting further interventions. But report to whom? Our first inclination may be the local institution where an experiment is taking place. There are, after all, typically internal mechanisms of oversight and investigation that could be triggered. However, if one has knowledge of an unethical experiment being conducted, it may be a sign that those mechanisms are not functioning properly. Reporting to the institution may then be inadequate to ensuring that the unethical research is stopped. One level higher would be national oversight bodies that have jurisdiction over where the research is being conducted. These would also have the advantage of enforcement power, as evidenced in the Chinese case when the government shut down He Jiankui’s study, or other means of penalizing such transgressions. Yet, individuals outside the country in question may be uncertain of the robustness of domestic oversight, what the appropriate body is, how far its investigational powers go, and so forth. A third option would be to inform journalists. It was, after all, scientific reporting that led to He Jiankui’s story breaking when it did. This option would maximize the chance of quick, public revelation and potential action. It has downside risks, though; although the scientific journalism in the He case was exemplary, in other cases journalists might not be so well equipped. Sensationalism or poor understanding of the underlying facts could cause substantial misunderstanding in international audiences, undermining the ability of the scientific community to earn trust in its enterprise. Leaving these matters solely to journalists would also suggest a serious lack of accountability in governance structures or mechanisms. Given the flaws with these options, we suggest that consideration should be given to the establishment of a new mechanism to receive and investigate reports of unethical human germline gene editing. This mechanism should operate at the international level because of both the possibility that potential reports come from outside the country where an experiment is occurring and the substantial international interest in responsible governance of human genome editing. The WHO is a natural locus for such a mechanism. Box 2 provides a sketch of a proposed structure for such a mechanism. Establishing a WHO-backed system may signal an expectation that reporting is indeed a responsibility of researchers globally. Additionally, the WHO has substantial influence that could help exert pressure on authorities to shut down unethical studies before they proceed too far. This was evident when, for instance, the Russian Ministry of Health justified its decision not to grant permission for a local germline intervention by referring to the current WHO position on the matter [11.Cohen J. Embattled Russian scientist sharpens plans to create gene-edited babies.Science. 2019; (Published online October 21, 2019. https://www.sciencemag.org/news/2019/10/embattled-russian-scientist-sharpens-plans-create-gene-edited-babies)Crossref Google Scholar]. An international reporting mechanism is not a panacea for preventing further premature, unethical germline gene editing experiments. Expectations of confidence in communications and the reputational cost of making a report would remain important problems that may require broader scientific cultural shifts. Additionally, there remains the possibility that individual countries would ignore international condemnation and would proceed with gene editing despite such a mechanism. Still, such a mechanism would at least remove a substantial barrier to reporting, facilitating those who want to uphold their responsibilities to report unethical conduct but do not see any straightforward mechanism for doing so. If a cultural shift toward recognizing this responsibility and avoiding complicity in wrongdoing is needed in the context of gene editing [12.Chen Q. et al.Making sense of it all: ethical reflections on the conditions surrounding the first genome-edited babies.Wellcome Open Res. 2020; 5: 216Crossref Google Scholar], the establishment of an international reporting mechanism by the WHO would be an important step in promulgating that norm and countering the culture of silence that currently pervades. 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 ).

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