This commentary was published in a 2017 Bioethica Forum special issue on Genome Editing as 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 Forum 10(2): 65-67. 

In the United States, the recently re-ignited debate about inheritable genetic modification has been strongly shaped by the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM), non­governmental organizations whose funding comes mostly from the federal government. In February 2017, a committee formed by NAS and NAM released a much ­anticipated report, Human Genome Editing: Science, Ethics, and Governance [1]. The 310-­page document, which made headlines in daily newspapers as well as scientific publications, recommended limita­tions on using gene editing for human reproduction, yet also concluded – in a striking departure from current widespread policy agreement, including legal prohibi­tions in dozens of countries as well as the Council of Europe’s Oviedo Convention – that “clinical trials using heritable germline genome editing should be permitted”.

The leaders of the committee that authored the report took pains to present it as a cautious and limited step. As MIT biologist Richard Hynes put it, “We say proceed with all due caution, but we don’t prohibit germline” [2]. Alta Charo, a bioethicist at University of Wisconsin­ Madison, commented that reproductive genome editing “is not ready now, but … if certain conditions are met, it might be permissible to try” [3].

Supporters of the long­-standing view that inheritable genetic modification should remain off­ limits evaluated the report differently. They emphasized both that the report represents a radical rupture with existing policy and public opinion, and that the stated intent to limit use of germline gene editing is unlikely to hold up. For example, the Center for Genetics and Society (CGS), a California­-based public interest organization with which the authors of this viewpoint are affiliated, re­sponded by stating, “Permitting human germline edit­ing for any reason would likely lead to its escape from regulatory limits, to its adoption for enhancement purposes, and to the emergence of a market-­based eugen­ics that would exacerbate already existing discrimina­tion, inequality, and conflict” [4].

Most media coverage of the report included both points of view, though with far more attention to the NAS/ NAM committee than to the scientists, bioethicists, and public interest advocates who criticized it. Also striking was the amount of confusion and uncertainty about what the report actually says and means. For example, while Science titled its story “US Panel Gives Yellow Light to Human Embryo Editing” [5], ArsTechnica chose “Genome­-edited humans get green light from ex­pert panel” [6]. Similarly, while Science quoted commit­tee member Jeffrey Kahn, a bioethicist at Johns Hop­kins University, as saying, “It’s frankly more of a knock on the door” [7], the Wall Street Journal titled its arti­cle, “Door Opens to Gene Editing in Embryos” [8]. Part of a larger trend, these examples reflect one of the major problems of the report: its ambiguity and vague­ness.

In this commentary, we briefly outline some of the main problems of the NAS/NAM report, and argue that it throws the door wide open for reproductive human gene editing, with serious implications.

Not as cautious as it claims

Just how cautious is the NAS/NAM report? What real­ world checks would its proposed restrictions provide? Let’s look at the very first item in the list of “criteria and structures” that  the report  recommends putting in place before clinical trials using heritable germline editing are permitted: an “absence of reasonable alternatives” [1, p. 7].

Most readers will assume this means that germline editing would be limited to cases in which all possible medical options for avoiding transmission of an un­wanted genetic condition to a future child had been exhausted. To those familiar with the germline modifi­cation debate, this refers to the availability and relative safety of the embryo screening technique known as pre­implantation diagnosis (PGD). Though PGD, like germline editing, raises concerns about which genes and traits will be socially valued or devalued, it permits nearly all prospective parents who carry unwanted genetic disease variants to have children who are un­affected and genetically related to them, without the additional physical and societal risks of manipulating genes in gametes or early embryos [9].

Since the report gives no definition of the criterion “ab­sence of reasonable alternatives”, one of us (Lowthorp) submitted a question to the panel of authors at the re­port’s official release event, asking whether it would be satisfied by a person with moral objections to PGD. Committee member Robin Lovell­-Badge of the Francis Crick Institute replied affirmatively that it would [10]. This is perhaps unsurprising, since other advocates of reproductive germline modification have ventured sim­ilar opinions, though none have addressed the questionable assumption that PGD would destroy more embryos than would gene editing. Lovell­-Badge’s reply illustrates that, at a minimum, the notion that the re­port’s recommendations would limit germline modifi­cations to a narrow range of cases is open to question. If an individual’s moral belief can override any limita­tions included in guidelines, the report is far less cau­tious than its authors claim.

Erasing a bright line

The NAS/NAM report is characterized by another problematic rhetorical strategy: it repeatedly acknowledges, and then dismisses or undercuts, a range of concerns about germline modification that have been central to the long­standing discussion of it. This is most evident and consequential in the report’s erasure of the bright line between somatic interventions that would affect existing patients, which are widely supported, and germline alterations that would be passed on to future generations, which are widely opposed.

One example of this acknowledge­ and­ dismiss strategy is the report’s mention of, but scant attention to, the Oviedo Convention. Signed by thirty-­five countries, the Convention establishes a clear distinction between somatic and germline interventions, prohibiting the latter. Despite the committee’s charge to “identify prin­ciples that many countries might be able to use to govern human genome editing”, its report refers to this key international treaty just twice in eight chapters – once in order to explain why it should not be considered influential [1, p. 132].

Another example can be found in a box titled “Making Distinctions” [1, p. 146]. Sketching a history of the clas­sic schematic counterposing somatic vs germline inter­ventions and therapeutic vs enhancement applications, the narrative briefly mentions the former while fore­grounding the latter. In stating that, “[b]y the mid­-1980s, scientists and bioethicists had begun to call for the morally relevant line to be between disease and enhancement rather than somatic and germline”, the report fails to acknowledge that this call represented a decidedly minority viewpoint worldwide, both then and now.

The report’s conclusion that germline editing should be permitted for therapeutic purposes replaces a bright line with one that most observers believe is conceptu­ally murky and impossible to regulate: therapy  vs enhancement [11]. The report itself references the “blurry boundaries of enhancement,” and concedes that this distinction is “not rigid or easily discernible in all cases” [1, p. 191, 192]. Similarly, it grants that “even the definition of what is considered a ‘disease’ can be open to debate” [1, p. 191] – though it nonetheless pairs “disease and disability” without caveat some two dozen times.

Denying democratic deliberation

The NAS/NAM report problematically departs not only from the laws of dozens of other nations, but also from a commitment recently made by the National Acade­mies themselves. In December 2015, NAS and NAM collaborated with the Chinese Academy of Sciences and the UK Royal Society to organize the “International Summit on Human Gene Editing”. At the end of the three-­day event, the Summit organizing committee is­sued a statement stipulating that it would be irrespon­sible to proceed with germline editing for reproduction unless and until a “broad societal consensus” had been reached [12]. The statement called for “an ongoing in­ternational forum … (that) should be inclusive among nations and engage a wide range of perspectives and expertise – including from biomedical scientists, social scientists, ethicists, health care providers, patients and their families, people with disabilities, policymakers, regulators, research funders, faith leaders, public inter­est advocates, industry representatives, and members of the general public”.

While the meaning of these provisions can and cer­tainly should be debated, the 2017 report dispenses with the idea of broad societal consensus altogether. Summit organizing committee member Françoise Bay­lis, Dalhousie University Professor and Canada Re­search Chair in Bioethics and Philosophy, observed that “with nary a word, the second element of the 2015 proposed ethics framework – broad societal consensus– has been jettisoned” [13]. In its place, the 2017 report substitutes its own judgment that germline gene editing should go forward, and limits public participation to questions such as which genetic modifications should or should not count as enhancements. In so doing, it effectively eviscerates democratic deliberation about whether human germline modification is acceptable in the first place.

Conclusion

In the instances sketched here and numerous others, the NAS/NAM report presents itself as cautious and incremental even while it radically shifts long­standing, internationally accepted policy conclusions and process commitments regarding human inheritable ge­netic modification. It repeatedly raises but then dismisses serious concerns – about the dubious nature of medical claims for germline gene editing’s utility; the inadequacy of a biomedical ethics framework for con­sidering a technology that could have significant social, cultural, and economic consequences; the unacceptable societal risk of creating a world of genetic “haves” and “have­-nots”; and the implausibility of a policy regime built on a blurry and subjective distinction between “therapy” and “enhancement”. The report mentions a robust range of evidence and argument, but without explanation gives dramatically less weight to anything that might disrupt its support for pushing ahead to­ward human germline modification.

Correspondence:
Marcy Darnovsky, PhD
Center for Genetics and Society 1122 University Ave. Suite 100
US-Berkeley, CA 94702
Email:  darnovsky[at]geneticsandsociety.org

References

1. National Academies of Science, Engineering, and Medicine. Human Genome Editing: Science, Ethics, and Governance. Washington, D.C.: The National Academies Press; 2017. Available at: www.nap. edu/read/24623/chapter/1 (accessed 5/9/2017).
2. Achenbach J. Ethicists advise caution in applying CRISPR gene editing to humans. Washington Post. 2017; Feb 14. Available at: www.washingtonpost.com/news/speaking­of­science/ wp/2017/02/14/ethicists­advise­caution­in­applying­crispr­ gene­editing­to­humans/?tid=sm_tw&utm_term=.907c6e637924 (accessed  5/9/2017).
3. Stein R. Scientific Panel Says Editing Heritable Human Genes Could Be OK In The Future. NPR. 2017; Feb 14. Available at: www.npr.org/sections/health­shots/2017/02/14/514580162/ scientific­panel­says­editing­heritable­human­genes­could­be­ok­ in­the­future (accessed 5/9/2017).
4. Center for Genetics and Society. New Human Gene Editing Report is Unsettling and Disappointing. Press statement, 2017 Feb 14. Available at: www.geneticsandsociety.org/press­statement/ new­human­gene­editing­report­unsettling­and­disappointing (accessed 5/9/2017); for additional perspectives, see Lowthorp L. Opening the Door to Genetically Engineered Future Generations: How the NAS Report Ignores Widespread International Agreement. Biopolitical Times. 2017; Feb 22. Available at: www.geneticsand society.org/biopolitical­times/opening­door­genetically­engineered­ future­generations­how­nas­report­ignores  (accessed  5/9/2017).
5. Kaiser J. U.S. panel gives yellow light to human embryo editing. Science. 2017; Feb 14. Available at: www.sciencemag.org/ news/2017/02/us­panel­gives­yellow­light­human­embryo­editing (accessed  5/9/2017).
6. Mole B. Genome­edited humans get green light from expert panel. Ars Technica. 2017; Feb 14. Available at: https://arstechnica.com/ science/2017/02/science­experts­endorse­genetically­editing­ humans/ (accessed 5/9/2017).
7. Hesman ST. Human gene editing therapies are OK in certain cases, panel advises. Science. 2017; Feb 14. Available at: www.science news.org/article/human­gene­editing­therapies­are­ok­certain­ cases­panel­advises (accessed 5/9/2017).
8. Dockser MA. Door Opens to Gene Editing in Embryos. The Wall Street Journal. 2017; Feb 14. Available at: www.wsj.com/articles/ gene­editing­could­be­permitted­under­certain­conditions­report­ says­1487112843  (accessed  5/9/2017).
9. See Lander ES. Brave new genome. N Engl J Med. 2015; July 2; 373:5­8.
10. See Lovell­Badge’s comment at 1:28:25 of the release event video here:  www.nationalacademies.org/gene­editing/consensus­study/ index.htm (accessed 5/9/2017).
11. See Baylis F. Human germline genome editing and broad societal consensus. Nature Human Behavior. 2017; May 8;1:1.
12. National Academies of Science, Engineering, and Medicine. On Human  Gene  Editing:  International  Summit  Statement. 2015; Dec 3. Available at: www8.nationalacademies.org/onpinews/ newsitem.aspx?recordid=12032015a&_ga=2.198854959. 1485407740.1504649118­131445906.1504649118 (accessed 5/9/2017).
13. Baylis F. Human germline genome editing: An ‘impressive’ sleight of hand? Impact Ethics blog, 2017; Feb 17. Available at: https:// impactethics.ca/2017/02/17/human­germline­genome­editing­ an­impressive­sleight­of­hand/  (accessed  5/9/2017).

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