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Bioethics Forum Essay

Engineering Consensus in the Development of Genome Editing Policy

In the past few weeks media outlets have been reporting on the release of Human Genome Editing: Science, Ethics, and Governance from the National Academies of Science, Engineering, and Medicine. The report concluded that following more research, it would be ethical to initiate clinical trials using heritable, germline genome editing for therapeutic purposes subject to a set of conditions. Described by some as a “fantastic development,” this declaration effectively lifted the nonbinding temporary moratorium from the International Summit on Human Gene Editing in 2015.

Although the lengthy report suggests extensive deliberation, it glosses over troubling scientific evidence pertaining to risks of gene editing and stands in stark contrast to the current widely held view in many countries against human germline modifications.

Scientists have referred to potential human germline modifications using gene editing tools as elegant, accurate, and precise, which connotes an exact application to correct a deficiency. This focus marginalizes the complexity of intervening environmental and other epigenetic factors, and presumes that editing technology constitutes the rational, and only, solution toward progress.

After all, who would want to cause “unnecessary misery” and prevent medical advancement?  Placing the ethos of suffering and survival at the forefront of the debate appeals to the very core of what we want from medicine and technology: better health, more certainty in prognosticating outcomes, and the deep primal yearning to have “healthy” genetically related children. The problem arises when the genomic model becomes the sacrosanct idol, and opposing it is attributed to misinformation and unsubstantiated fears.

In the past few years, scientists and bioethicists have discussed the serious potential risks involved with gene editing, such as mosaicism, off-target effects, and incomplete editing.  Last July, Stat News highlighted growing evidence that there may be more off-target effects that originally predicted. Discussion of potential errors presumes that scientists have sufficient information to target the correct part of the genome to “fix.”  However, biologist Stuart Newman  has suggested that this preliminary assumption may not be correct, because variants classified as pathogenic may not be harmful in all individuals.

These limitations reinforce what many scientists and scholars have observed: that germline modifications will always carry a margin of risk. The question then becomes, who the policy discussions accurately characterize the weight of the scientific evidence and explore nuances contained in that model of risk?  Recently, the United States approached a similar quandary, whether to permit germline modification via mitochondrial replacement therapy. Unlike some who have praised this model as a pathway to inform gene editing, I see troubling parallels between the policy evolution of mitochondrial replacement therapy and gene editing, which should give us pause.

Back in 2014, scientists convened before the FDA to discuss mitochondrial replacement therapy, describing the inability to predict safety and assess latent risks and listing potentially insurmountable hurdles arising from intricacies of mitochondrial biology. Numerous statements from participants cautioned against the lack of evidence pertaining to safety and efficacy, the potential to cause abnormalities, and the gravity of risk involved.  Despite these warnings based on scientific considerations, the National Academies of Science, Engineering, and Medicine recently concluded that conducting clinical trials for mitochondrial replacement therapy is ethically permissible. Although the process for both mitochondrial replacement therapy and gene editing provides the appearance of deliberation, it reveals a disconnect between the state of the science and the characterization of the science while obscuring likely motivational drivers: the pursuit of scientific prestige and capturing a highly lucrative commercial market.

Presuming the inevitability of gene editing in the U.S. also fails to situate our nation within the international context.  Many countries, including Canada, Germany, France, Switzerland, Sweden, and Italy, have adopted legislation prohibiting germline intervention on human embryos for implantation. In some of these nations, germline modification constitutes criminal violation subject to fines and or imprisonment. Prohibiting and criminalizing an action communicates its egregiousness, potential for harm, and social unacceptability in these nations  Unlike the alarmist rhetoric that the U.S. is falling behind and failing to invest in promising genomic technologies, these laws demonstrate the opposite: many countries acknowledge the lure of technology, but renounce risky experiments that cross the historical bright line of manipulating future generations.

As UNESCO’s International Bioethics Committee  has cautioned, neither professional accolades nor market forces should drive the adoption of genomic technologies.  It is crucial to not only step back to assess chasm between the very significant risks pertaining to germline modification and the National Academies current stance, but also to ask why the policy deliberations have been so swift to affirmatively declare that the benefits would outweigh these risks in future clinical applications.

Katherine Drabiak, JD, is an assistant professor in the College of Public Health at USF Health at the University of South Florida.

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