by Christopher Thomas Scott, Ph.D. and Cynthia Selin, Ph.D.
In the wake of reports that a Chinese biophysicist, He Jiankui, used a genome editing technology, CRISPR/Cas9, to modify the CCR5 gene in viable human embryos, the criticism from the international scientific and bioethics communities has been swift and unrelenting. The overwhelming conclusion is that Dr. He’s procedure was deceptive, violated Chinese law, flaunted international ethical norms and put the babies at physical risk. It was, simply put, unethical human experimentation. Dr. He has since disappeared, raising the question whether the experiment was a hoax. The long shadow of Hwang Woo-suk—the infamous human cloning fraudster—is now cast upon the scene.
Hwang’s ersatz experiment, which he dropped at the 2004 International Stem Cell Society annual meeting, was a bolt from the blue. Technical hurdles, including overcoming the species barrier, had for years flummoxed researchers attempting to use somatic cell nuclear transfer (SCNT) to clone primate embryonic stem cell lines. Yet He’s CRISPR babies hardly came as a surprise. Telltales were apparent as early as 2013 when a Chinese team reported generating rats using the technology (Li et al. 2013). In January 2014, a different group in China reported twin cynomolgus monkeys born with mutations made with CRISPR/Cas9 (Niuet al. 2014).1These experiments foreordained the eventual application of the technology in human embryos. Although it wasn’t until 2016 that two essays by scientists, inventors, and bioethicists in the journals Natureand Sciencedetailed recommendations for how future human germline research should proceed (Lanphier et al. 2015; Baltimore et al. 2015), the future had rushed ever closer: Chinese experiments using human embryos were reported on the heels of the essays. Using CRISPR in nonviable human embryos, one research team knocked out the human gene HBB, while another introduced CCR5, an HIV-resistance allele (Liang et al. 2015; Kang et al. 2016). A third experiment in the U.S. successfully corrected a mutation causing heart disease in viable human embryos, which were later destroyed as part of the protocol (Ma et al. 2017).
Despite the speed of innovation, there has been a marked slowness of ethical reckoning for how we should responsibly adopt genome editing. After an initial 2015 summit, the National Academyof Sciences, Engineering and Medicine (NASEM) published its report and recommendations on human genome editing in March 2017. The report describes application of existing regulatory structures to possible future uses of genome editing technologies, and opened the door to germline applications in narrow therapeutic cases, and then only after more research had determined it was safe. The nearly 300 pages of expert advice—done in partnership with China—didn’t guard against what would happen next. In Hong Kong, exactly three years after the first summit, Dr. He reported the birth of CRISPR-engineered twins, with a third baby possibly on the way. David Baltimore, one of the architects of the Hong Kong meeting, the lead author of the 2015 Science essay, and an organizer of the famed Asilomar Conference over 40 years earlier, said He’s experiment was a “failure of self-regulation” by the scientific community (Cohen 2018). A disruptive new technology—already six years in the making—had somehow outrun the ability of scientists, policymakers and ethicists to responsibly govern it.
Policymaking that can better anticipate and prepare for these challenges is urgently needed, and the He experiment underscores that we do not have the luxury of another six years of wait-and-see. Over 30 years ago, David Collingridge described a procedural paradox associated with social control over new technologies (Collingridge 1980). During the early phases of development, it is difficult to predict the impact of emerging technologies. But during the later phases, after undesirable consequences have been discovered, the new inventions have already become locked into specific trajectories, making it extremely difficult to manage future applications or alter course. In response to this problem, various strategies to help steer new genetic technologies have been attempted, such as the response to engineered, super-infective strains of flu virus or public acceptability of field trials of genetically modified animal vectors. However, these strategies can suffer from a lack of institutional leverage, sluggish policymaking, a reactionary stance, and a failure to effectively engage citizens with scientists early in the technology development process (Jasonoff 2015; Juengst 2017; King 2017) A structured and replicable approach is needed to better prepare the institutions governing emerging technologies for the consequences of human genome editing.
Anticipatory governance (AG) has emerged as a way to deal with the social control of new technologies associated with the Collingridge Dilemma (Barben et al. 2017). At the core, policies are about articulating values and limits. AG explicitly includes ethical reckoning and direct engagement with diverse stakeholders, including the lay public. Currently, little is known about how human genome editing maps onto public attitudes, and what we do know of public opinion about germline editing is limited to surveys on U.S. and international beliefs (Funk and Hefferon 2018; Scheufele et al. 2017; Gaskell et al. 2017; Funk et al. 2016). While the public generally favors therapeutic uses over human enhancement, the U.S. survey reveals a clear mandate for deeper and ongoing public engagement (Scheufele et al 2017). AG further prescribes the creation of a capacity to systematically explore the layers of uncertainty that arise from novel technologies and their interface with changing social and ethical norms (Guston 2014;Barben et al 2017). Foresight methods offer a way to posit plausible alternative futures in order to proactively prepare for different outcomes. When the past is not a reliable guide to the future—as in the case of human genome editing—using foresight in both expert and public deliberations can uncover and confront unpredictable uncertainties in order to make better, more robust, governing decisions.
The genome editing report acknowledges that moving forward will require both anticipation and public engagement, and Dr. Baltimore repeated this mantra in Hong Kong. Two other NASEM reports wrestling with emerging genetic technologies—gene drives and mitochondrial transfer— echo these recommendations and the gene drive report is explicit in the use of AG as a governance strategy (NASEM 2016a;NASEM 2016b). As these technologies develop, the genome editing report states, there will be a need for ways to “deal with both facts and values and in particular with how anticipatedchanges in the world will affect the things people value” (emphasis added) (NASEM 2017, 245). Deliberative engagement can address “the need for ongoing public discussion about how regulatory bodies should draw distinctions between such things as therapy and enhancement or disability or disease” (NASEM 2017, 143). It allows members of the lay public to ask questions and suggest solutions that may not have been imagined by regulators or experts.
Expert committee work, including work performed by NASEM, has long been a go-to method for U.S. science policy. The strength of this method lies in the expertise of the individuals who constitute such committees. While committees use a variety of mechanisms to elicit public input to inform their decision-making, these mechanisms may be insufficient to the purpose of deliberative democracy, where “imagining what is right and appropriate for our world—and what threatens its moral foundations—is a task for democracy, not for science” (Hurlbut 2015, 12). The human genome editing report admits that while opportunities for public engagement exist at the federal level, they “tend to be limited and passive, and not the fuller public engagement that may be appropriate for an important new technology such as genome editing” (NASEM 2017,130). It further notes that “important questions raised with respect to gene editing include how to incorporate societal values into salient clinical and policy considerations” (NASEM 2017,155). In the end, imaginations of the future are socially constructed, and so the absence of meaningful input from the public on the trajectories of science appears to be a major limitation of the expert governance model.
Policymaking armed with a quiver of anticipatory tools has a certain allure, for policy made with adequate foresight would have profound and potentially beneficial downstream consequences, whether it is declaring socially problematic research off limits, prioritizing funding for pressing biomedical questions, or simply being better prepared for what awaits us. What we hope to encourage is an increasing array of anticipatory strategies that are purpose-built for the rapid changes afoot. Out of our collective imaginings will come actions we can take now—some small, some large—to forge better futures.