The CRISPR Fantasy: Flaws in Current Metaphors of Gene-Modifying Technology

The August 2015 edition of Wired magazine is wrapped in literary gold. The front cover, promoting an enclosed article by Amy Maxmen about CRISPR genetic engineering technology, launches cinematic claims that sear the retinas of scientific bookworms: “PLAY GOD. No hunger. No pollution. No disease. And the end of life as we know it. The Genesis Engine. Editing DNA is now as easy as cut and paste. Welcome to the post-natural world.” The wonton verbosity, continued in the actual article, was not lost on readers. The Twittersphere swelled with satirical #crisprfacts: “CRISPR makes the Most Interesting Man in the World more interesting,” “If you apply CRISPR to Joyce’s Ulysses, you discover it is really a short story by Hemingway,” and “’You must be the change you want to see in the world.’ ~CRISPR” (Harrington, 2015, para 6). However, while the rhetoric may not always be so outwardly bombastic, nearly every reference to CRISPR induces some sense of fantasy.

Indeed, when describing foreign biological terms, introducing familiarizing metaphor is almost certainly needed to establish a basis for understanding. Moreover, due to this device’s ubiquity, figurative terminology has become deeply embedded in both scientific and popular discourse. User-friendly framings are especially evident with technologies commanding esoteric full names, like Clustered Regularly Interspaced Palindromic Repeats (CRISPR).

Layers of factual oversimplifications impede effective and ethical descriptions of this genome engineering technology’s true capabilities.

As Nelkin, a renowned sociologist specializing in the relationship between scientists and the public, generally states in Nature (2001), “Unfamiliar and frequently technical material [is represented] most effectively through images that are chosen for their richness of reference” and “their familiar meanings;” they shape “the ways we perceive” subjects and “our attitudes” (p. 556). However, with great power comes great responsibility. The current metaphors that mold perceptions of CRISPR—commonly described as a gene-editing tool—are flawed. Layers of factual oversimplifications impede effective and ethical descriptions of this genome engineering technology’s true capabilities.

As any literary artist knows, superficial presentations make deep impacts. The subtle connotations underlying descriptory language shift how readers approach a given topic. In the case of CRISPR, I will methodologically elucidate the conceptual mismatch between subjective presentation and neutral reality. After briefly introducing the biomechanics of CRISPR and metaphor theory, I engage the blooming bioethical-linguistic debate over CRISPR technology to evidence imperfections in current metaphors, integrating theoretical foundations with primary analyses of media sources.

Then, to contextualize my argument, metaphorical efficacy is connected with public policy and recent advancements in biotechnology. The truthfulness of a given term displays time-dependency. If reality changes, so does the accuracy of the associated terminology. Finally, after identifying the problem and its implications, I transition to the solution process. I propose that while public audiences and bioethical linguists play a vital role in providing criticism, the actual power to evaluate and update metaphors rests in the hands of scientists.

Identifying Glitches in the Modern Metaphorical Machine

The term CRISPR itself has undergone a massive semantic shift. Doudna and Charpentier, the forefather scientists who brought CRISPR to mainstream audiences, begin their keynote review by explaining how the extended name, Clustered Regularly Interspaced Palindromic Repeats, stems from an ancient E. Coli defense mechanism that utilizes repeated DNA sequences (CRISPRs) and Cas9 cleavage proteins (2013). In the late 2000s, they had a groundbreaking realization: By equipping naturally occurring bacterial Cas9 scissor proteins with human-synthesized single-stranded RNA guides, sgRNAs, the microbial CRISPR-Cas9 system (colloquially shortened to CRISPR) could be repurposed by scientists to target and slice organisms’ DNA sequences at any desired location. A molecular scalpel.

Combined with pre-existing donor DNA introduction techniques, segments of the genome can be inserted and deleted with relative ease. Moreover, recent developments in attaching DNA activator and repressor bricks to Cas9 allows for turning genes on and off. With this easy, cheap streamlined process, $160 in pocket money enables novice biohackers to purchase a kit and start editing genetic code (Loz, 2016).

What is metaphor? Metaphor is “understanding and experiencing one kind of thing in terms of the other”

As exemplified in the previous statements, metaphors (italicized) are immensely useful for communicating technical science. But, at heart, what are metaphors, and what fuels their power? O’Keefe et al., who ignited the CRISPR-specific conversation in 2015, defines metaphor as “understanding and experiencing one kind of thing in terms of the other” (p. 4). This enables “people to acquire new knowledge by linking terms and concepts to the familiar;” however, in the words of O’Keefe and colleagues, scientists should aim for “metaphors that accurately capture the complexities of the ethical issues involved in CRISPR” (p. 3). Why? Because as education professor Jack Lumby states, misleading metaphors have “the power to manipulate, to shut down thinking, to deflect creativity” (2010, p. 3).

In other words, they constrain understanding by projecting a restricted point of view. Applying the ideas of prominent linguist George Lakoff, metaphorical framings of topics, ubiquitous and often implicit, massively shift readers’ perspectives for better or worse (Lakoff & Johnson, 1980). O’Keefe and colleagues use a three-armed scale to assess the current figurative devices by their abilities to convey “(1) the ethical complexity of the technology,” “(2) an accurate description…how it works and how it can be used,” and “(3) what is known and unknown about its potential consequences” (p. 4). O’Keefe et al. believes that “current predominant metaphors [about CRISPR] miss all of these” (p. 4). I adopt a similar but more nuanced stance: The current metaphors deliver one-sided representations of reality, but evaluation must be conducted with a time-sensitive mindset to address linguistic complications imposed by historical precedence and future technological advances.

“If you genetically edit the lettuce genome, you can make it CRISPR #crisprfacts” (Harrington, 2015, para 6). Indeed, even the term’s homonym, “crisp-er,” effuses an aura of freshness and precision (Zimmer, 2016). It only makes sense that founding scientist Jennifer Doudna “likened it to microsurgery” (O’Keefe et al., 2015, p. 7). The leading metaphors—“editing,” “cutting and pasting,” “targeting,” “snipping out”—fabricate a pseudo-truth of precision and accuracy: Editing is a misrepresentative oversimplification, for Cas9 is a complex biological molecule operating in an even more complex environment (O’Keefe et al.).

Even with revolutionary science, I anticipate experimental mistakes. The genomic structure is too variable to be a solid-state text and the enzymatic CRISPR system is too multilayered to be a machinated editor—if this simplicity were reality, introductory biology textbooks wouldn’t need chapter upon chapter to cover gene packaging and protein function. Another common phrase, gene targeting, invokes precision through different means by recalling notions of 21^st century honing projectiles (O’Keefe et al.). Even the critically phrased off-target results, describing when Cas9 accidently cuts the genome at the wrong location, is deleterious—off-target deceptively insinuates unrealistic error minimization techniques. Overall, controlling diction is applied to imperfectly controlled technology.

Linguistic techniques, like scientific techniques, contain many subtleties. In fact, closely analyzing the grammatical structure of commonly considered phrases like editing and targeting further emphasizes their flaws. Specifically, the “true” metaphor for CRISPR is not editing but the editor. Linguist Nelson et al. points out that O’Keefe et al.’s editing describes CRISPR’s actions, not CRISPR itself; the underlying implicit metaphor holds CRISPR as a human-operated “word processor,” thereby bolstering the idea of direct human control (2015, p. 61). I find this concept fortifies the misplaced notion of CRISPR as an operable machine. Again, metaphorical accuracy is impacted by a horde of nuances, one being a grammatical constraint. Verbs represent verbs. Nouns represent nouns. Important interpretive implications results.

Subtleties, however, can extend beyond microscopic analysis and reach back into ancestral roots. I show these roots to bind current conversations in historical constraints. As Nelson et al. states, if one “sufficiently distinguish[es] between [the] two tenors [CRISPR and genome],” there is “the opportunity to make explicit how the [more widespread] genome metaphors are potentially shaping and constraining the CRISPR metaphor[s]” (2015, p. 61). Classic phrases, like the DNA Book of Life, leech into new technological terminology. As evidence of this phenomena in our daily lives, media portrays CRISPR merely as editing a set genetic script, the spiritual descendant of the Holy Book. New structures are built upon misplaced foundations. Mistakes of old genetic metaphors, which bioethics expert Nordgren states are “reductionist, essentialist, and deterministic,” are inherited (2001, p. 107).

To exemplify this, a decade ago, DNA was said to dictate an organism’s traits and destiny. Applying this idea to modern times, altering the codified Holy Grail with CRISPR will intrinsically change an organism’s makeup and future. This ties into O’Keefe and colleagues’ ideas of oversimplification and misrepresented control. Cumulating constraints spark a conceptual chain reaction: Precisely editing genes leads to precisely editing individuals leads to precisely editing futures. Cut and paste. Test tube babies. In the words of Wired, “Welcome to the post-natural world” (Maxmen, 2015, cover). For now, however, Wired’s “science fiction storyline” is just that: Fantasy (Pauwels, p. 524). Nordgren’s complex biological interactions at “higher levels of organization” have not been completely mastered by scientists (p. 108). While subject to change, I can only design embryos in a fictional thought experiment. In summation, old genome metaphors constrain new CRISPR rhetoric, grammatical power structures constrain metaphorical devices, and on a whole, the current texts surrounding genetics constrain effective portrayal of CRISPR’s real capabilities. This results in a comprehensive system of literary convolution.

The difficulty in navigating this metaphorical web is perfectly evidenced in a 2015 mass media Guardian article titled, “Crispr: is it a good idea to ‘upgrade’ our DNA?” Overall, author Zoe Corbyn highlights major developments in medicinal CRISPR applications while warning against hasty actions in human genome editing due to the potential of unintended mistakes. However, despite cautioning against technological recklessness, Corbyn’s oversimplifying word choices have the opposite effect. Upgrade is commonly associated with software updates and hardware advancements. Controlled forward progress is expected. In this case, the CRISPR-machine analogy is blatant, with Corbyn describing how “Genome-tinkering machinery” is deployed to bring about therapeutic effects (para 7). For an article that mainly questions whether performing CRISPR techniques on living organisms can be done “accurately and safely,” Corbyn unabashedly uses terms like gene settings, scissors, and of course, editing (para 26). Connotative terminology subconsciously undermines the macroscopic premise.

Corbyn is not at fault. Indeed, even Doudna and Charpentier’s hallmark paper described how CRISPR could be used to “target, edit, modify, regulate, and mark” (2014, p. 1). The terminology is deeply embedded in discourse. However, this raises an important counterpoint. Some linguists, like Pinker, argue that commonplace metaphors have lost their figurative potency (2006). Under this viewpoint, editing and targeting are essentially “dead metaphors…concepts which have become so familiar and so habitual in our theoretical vocabulary that… we [have] ceased to be aware of their metaphorical precepts” (Cornelissen, 2002, p. 261).

However, can they still have an impact on readers? According to Lumby (2013), they do: “Dead metaphors have the capacity to shape thinking and values as much as those that are live… [by] reflecting a worldview” (p. 5). I can accept that edit and target are so ubiquitous, they might be dead, but unlike Pinker, I assert the dead have great power. Edit and target may not consciously render as metaphors, but they still present CRISPR in a frame of machine-esque control. Sure, molecular scalpels and fine-tuned scissors hold flamboyant flair, but the implicit impressions left by the silent dead shape how we approach conversation. The editing framework subconsciously and one-sidedly nudges us towards a precision-based perspective. Thus, dead metaphors are even trickier than their overt counterparts—even when selecting terms for neutrality, dead metaphors worm their way into writing due to lack of perception.

The varied presence of metaphors, both dead and alive, is evidenced in a rhetorical analysis of two Nature press publications by Dr. Heidi Ledford. In a June 2015 publication, “CRISPR, the disruptor,” Ledford warns that with a powerful technique like CRISPR, whose edits to the genome can transcend generations, regulatory precautions are essential. It is common sense that rectifying multi-gene disorders through mass modifications may result in lethal repercussions. Besides ubiquitous dead metaphors like editing and targeting, Ledford abstains from noticeably bombastic devices in her criticism-based article. However, in her later March 2016 publication titled “CRISPR: gene editing is just the beginning,” her writing intent shifts from caution to praise.

Likewise, all metaphorical stops are pulled, with usage of “molecular machinery,” “scalpel,” ”biological circuits,” “turn genes on and off,” and “modified scissors” (p. 157). To evoke excitement instead of wariness, Ledford favors idealistic and impressionable phrases. I emphasize this switch of metaphorical vocabulary in differently-geared articles to showcase the influence of language in perception. In further analysis, applying the ideas of Lumby, the subconsciously-connotated editing and targeting impose hidden meaning constraints in both of Ledford’s works. While some metaphorical modulation is implemented deliberately by the writer for rhetorical control, it is clear that the frames of dead metaphors innervate nearly all literature.

Addressing another counterpoint, Ben Merriman, a linguistic commenter on CRISPR, argues that the constraint of current leading metaphors like editing and targeting are beneficial. After describing his argument, I will selectively refute and complexify the claims. Merriman argues that with CRISPR technology rapidly becoming more “reliable, inexpensive, and widely diffused,” figurative devices should be primarily judged by their power to influence ethical usage of biotechnology (2015, p. 62). Merriman finds that current metaphors facilitate proper regulatory discussion. For example, he proposes that editing the genetic code ideologically imports pre-existing computational regulations and that targeting’s war-cries subtly caution readers about CRISPR becoming a dual-use technology (military and civilian usage). Thus, genomic information security issues and potential bioweaponry applications can be framed in current legislative restrictions for these fields. However, Merriman does not address how updated metaphors will fail to meet his criteria.

For example, to better represent dynamic cell systems, O’Keefe et al. recommends “ecological metaphors” that capture the complex “role played by environmental factors” (2015, p. 8). Editing one node in a gene network affects its surrounding connections in endless, and sometimes unanticipated, ways. Does such an improved metaphor not import ecological regulation? Or computational network restrictions? Also, as genetics is directly connected more and more to computational science and bioweaponry, won’t the preexisting regulations for these fields be imported regardless of metaphorical usage? The merits Merriman imparts to current metaphors will still hold true whether improvements occur or not.Continued on Next Page »