GENEWATCH
 
THE EVOLVING STATE OF HUMAN GERMLINE EDITING
By Katie Hasson
 

from GeneWatch 31-1 | Jan-July 2018

A wave of controversy about reproductive gene editing gathered force in response to reports in 2015 of the first CRISPR experiments on human embryos. That news provoked two kinds of reactions: on the one hand, hyperbolic claims about "editing humanity" and the new ability to "engineer the human race"; on the other, deep concern, calls for moratoria (if not outright prohibition), and reaffirmations of national and international prohibitions of germline modification.

The tone has shifted considerably since then. While grandiose ambitions for reproductive germline editing can still be heard, some proponents seem to be playing them down, perhaps in an effort to calm public concern.

Yet media coverage of recent embryo editing studies has been largely celebratory. Very few scientists have been openly critical, and calls to "reconsider" some of the longstanding global consensus documents prohibiting germline editing are gaining steam.

One notable aspect of the current debate on reproductive germline editing is the widespread recognition that decisions about it can't be made by the small professional bodes and expert committees that have dominated the conversation up to this point. Most participants have called for "broad societal consensus," "public participation," or the like. Recently, several new groups have proposed concrete ideas for public engagement.

This article summarizes recent technical and policy developments regarding human germline editing, with a focus on assessing the conversation about the conversation - that is, asking whether the proposals for public discussion are sufficient to encouraging meaningful public engagement and empowerment.

Technical developments

In 2017, four papers on human embryo editing were published, bringing the total up to six. This included the first experiments on viable human embryos from a lab in China,[1] the first embryo editing work in the US by Shoukrat Mitalipov at Oregon Health and Sciences University,[2] and the first publication from Kathy Niakan's research in the UK.[3]

Mitalipov's research, in particular, received heavy and mostly laudatory media attention, in part because it was the first embryo editing research reported in the U.S. and in part because he claimed to have accomplished high rates of success with almost no off-target effects or mosaicism. However, prominent scientists in the field raised serious doubts about his research claims that he has not answered to date, and subsequent research findings seem to support their critiques.[4]

The celebratory headlines and media hype were striking and disturbing, particularly in comparison with the coverage from just a few years ago.[5] In fact, in early 2018 another embryo editing study[6] was published and received no media attention at all. Strangely, this normalization of embryo research is happening even as we see the publication of more and more studies showing that CRISPR has serious limitations in terms of efficacy and accuracy and carries significant risks for use in humans. For example, recent research shows that CRISPR's on-target effects may be less accurate than believed, resulting in a sort of "genome vandalism" with potentially risky results.[7] It's too soon to know how much of a barrier these technical challenges will turn out to be, but they make clear that it is far too soon to consider gene editing "safe."

Policy developments

Also new over the past 18 months are several significant policy reports and position statements. Both the U.S. National Academies of Sciences, Engineering, and Medicine and the UK's Nuffield Council on Bioethics released the human gene editing reports they had been working on for the past several years.

The NAS report, published in February 2017, recommended moving to clinical trials with human germline gene editing in certain limited circumstances.[8] Limitations notwithstanding, this represented a radical and dangerous departure from the long-standing international consensus that interventions in the human germline should remain off limits.[9] It also constituted a reversal of the recommendation that the NAS itself made just over a year earlier, that moving forward with this technique in humans would be irresponsible without first establishing a "broad societal consensus."[10]

Last year was also the 20th anniversary of the Council of Europe's Oviedo Convention, a binding international treaty that includes a prohibition of heritable human genetic modification. The anniversary prompted calls for remaining countries to ratify Oviedo as well as individual calls to revisit or revoke its prohibition of heritable genetic modification.[11]

The Nuffield Council report, released just this month, arguably goes further than any previous advisory body in endorsing the use of reproductive germline modification.[12] The report concludes that reproductive germline editing for any purpose could be "morally permissible" as long as it is in the future child's best interest and does not increase societal inequality or discrimination. Notably, Nuffield dispensed with the common arguments (embraced by NAS) that germline gene editing could be considered "therapeutic," that the line between therapy and enhancement could be clearly determined, or that there is a significant distinction to be made between basic and clinical research. While for most observers these accurate assessments suggest the need for great caution if not outright prohibition, the Nuffield report concluded otherwise. The clarity of these points makes its permissive recommendations even more distressing.

New calls for public engagement

But there are also some promising developments on the horizon, as groups and individuals put sustained thought into how we might develop and facilitate the kinds of public participation that could generate broad societal consensus on the question of reproductive gene editing. Even the Nuffield Council report calls for developing an "independent body... to promote and coordinate societal debate on genome editing."[13] What these efforts have in common is their recognition that getting to broad societal consensus will require committing significant financial and institutional resources to developing and facilitating meaningful public participation.

The Association for Responsible Research and Innovation in Gene Editing (ARRIGE) launched in March 2018 and currently has over 400 members.[14] Their stated aim is to promote global governance of genome editing with input from a wide range of stakeholders (academics, private companies, patient organizations, citizens, decision makers). Thus far they exist mostly online, and it's unclear what shape the organization will assume or what kinds of positions they might take. The enthusiastic support for human germline editing among a few of the founders suggests a pro-germline stance. Calls to revisit Oviedo and other international bans that were made in an earlier, pre-launch paper by the group's founders also support this view.[15] However, subsequent discussions taking place in the group reveal that these views are not universally held.

Around the same time, another group of scholars and scientists, organized by Sheila Jasanoff and Benjamin Hurlbut, put forth a proposal for a "Global Observatory" for gene editing.[16] The main function of the proposed observatory would be "to expand the range of questions that need to be addressed by making visible the diversity of moral perspectives represented within the global human community." They are not proposing to give specific advice on whether or how to proceed with particular uses of gene editing, but rather to outline what it would take to achieve a truly "broad societal consensus." This would begin with involving the broadest possible range of participants and perspectives, as well as providing infrastructure to facilitate the public deliberations that are necessary. Most importantly, they argue that the range of questions offered for public deliberation should not be constrained in advance - any attempt at societal consensus on germline gene editing ought to start with discussion of what is at stake and what questions need to be answered.

As the authors point out, this will require ways of listening to and learning from a broad range of thinking about moral and social values, what they call a cosmopolitan ethic. One resource for doing this - which they unfortunately underemphasize - is the rich landscape of existing civil society organizations that already undertake concerted efforts to ensure social justice, human rights, and the public interest. Connecting the movements and missions that these organizations pursue to the stakes and questions surrounding gene editing should be a priority.

The current moment

What can we make of these opposing trends in the gene editing conversation: seeming normalization in scientific and policy discussions, alongside intensified calls for engaging the public? And how can we ensure that debates about germline editing result in empowered public participation with meaningful results?

Public deliberation can only be meaningful if we resist the move to make technical questions around safety and efficacy stand in for broader and deeper discussion about social and ethical values. Gene editing debates can't remain a closed loop among small groups of scientists and bioethics professionals.[17] We've already seen instances in which scientists who are eager to move germline editing into the clinic see the NAS report as providing ethical cover for their work. Meaningful public engagement requires (at the very least) a pause in efforts to pursue germline editing to prevent rogue or overeager scientists from making this fateful decision for the rest of humanity.

Katie Hasson, PhD, is Program Director on Genetic Justice at the Center for Genetics and Society.

 

ENDNOTES

1. https://link.springer.com/article/10.1007%2Fs00438-017-1299-z

2. https://www.nature.com/articles/nature23305

3. https://www.nature.com/articles/nature24033; https://www.geneticsandsociety.org/biopolitical-times/editing-human-embryos-research-do-intentions-matter

4. https://www.biorxiv.org/content/biorxiv/early/2017/08/28/181255.full.pdf; http://www.nature.com/news/doubts-raised-about-crispr-gene-editing-study-in-human-embryos-1.22547

5. https://www.geneticsandsociety.org/biopolitical-times/7-questionable-claims-reporting-gene-editing-human-embryos; https://www.geneticsandsociety.org/biopolitical-times/embryos-and-spin

6. DOI 10.1002/mrd.22983

7. https://www.nature.com/articles/Nbt.4192; https://www.statnews.com/2018/07/16/crispr-potential-dna-damage-underestimated/;  https://www.statnews.com/2018/07/17/crispr-study-stocks/

8. https://www.nap.edu/catalog/24623/human-genome-editing-science-ethics-and-governance

9. https://www.openglobalrights.org/reproductive-gene-editing-imperils-universal-human-rights/

10. Lowthorp, Leah and Marcy Darnovsky. 2017. Reproductive genome editing and the U.S. National Academies Report: knocking on a closed door or throwing it wide open? Bioethica Forum10(2); https://www.geneticsandsociety.org/biopolitical-times/opening-door-genetically-engineered-future-generations-how-nas-report-ignores

11. http://semantic-pace.net/tools/pdf.aspx?doc=aHR0cDovL2Fzc2VtYmx5LmNvZS5pbnQvbncveG1sL1hSZWYvWDJILURXLWV4dHIuYXNwP2ZpbGVpZD0yNDIyOCZsYW5nPUVO&xsl=aHR0cDovL3NlbWFudGljcGFjZS5uZXQvWHNsdC9QZGYvWFJlZi1XRC1BVC1YTUwyUERGLnhzbA==&xsltparams=ZmlsZWlkPTI0MjI4 ; https://www.geneticsandsociety.org/biopolitical-times/cgs-oviedo-conventions-20th-anniversary

12. http://nuffieldbioethics.org/project/genome-editing-human-reproduction

13. http://nuffieldbioethics.org/wp-content/uploads/Genome-editing-and-human-reproduction-short-guide-website.pdf

14. http://arrige.org/; https://www.liebertpub.com/doi/10.1089/crispr.2018.29012.mon; http://www.sciencemag.org/news/2018/03/interested-responsible-gene-editing-join-new-club

15. https://link.springer.com/article/10.1007%2Fs11248-017-0028-z

16. https://www.nature.com/articles/d41586-018-03270-w; https://www.sciencedirect.com/science/article/pii/S0167779918301227; https://www.sciencedirect.com/science/article/pii/S0167779918301215

17. http://www.zocalopublicsquare.org/2018/01/17/designer-dna-isnt-just-designer-babies/ideas/essay/

 

 

 

 
 
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