CRISPR-Cas9 is complicated.
That’s why scientists, entrepreneurs, and journalists like me have spent the past few years reaching for metaphors to try to make the mechanics of the revolutionary genome-editing technology easier for laypeople to understand. In text and imagery, we’ve drawn parallels to everything from garage tools to divine interventions.
But it must be said: Some of these analogies are better than others. To compile the definitive ranking, I sat down with STAT’s senior science writer Sharon Begley, a wordsmith who has herself compared CRISPR to “1,000 monkeys editing a Word document” and the kind of dog “you can train to retrieve everything from Frisbees to slippers to a cold beer.”
Sharon and I evaluated each of the metaphors we found by considering these three questions: Is it creative? Is it clear? And is it accurate? Below, our rankings of CRISPR analogies, ordered from worst to best:
A knockout punch
Click https://t.co/UkfimtmfRl for a CRISPR Special Edition of 2016 landmark papers from Cell. #CRISPR #Nature #CellPress #biotechnology pic.twitter.com/lJJF95dKap
— OriGene (@origenebio) October 14, 2016
This is not how it works. This is not at all how it works.
We see where these marketers got started with their pun: Genetics researchers do indeed use the term “knock out” to refer to eliminating an existing gene in, say, a mouse.
But a blunt instrument like a boxing glove vastly undersells CRISPR’s precision. It also suggests, wrongly, that CRISPR’s powers extend to leaving genes bruised and battered. For these reasons, this ad wins the ignoble prize as the worst CRISPR metaphor we could track down.
The hand of God
CRISPR gene editing tool: Are we ready to play God? https://t.co/EN6wLOKoVE
— USA TODAY Tech (@usatodaytech) July 30, 2017
The hand of God is a familiar trope to describe advances in biotech. Elucidating CRISPR this way is sinful.
If God were in the business of editing the genome, we expect that She would make fewer mistakes than CRISPR, which is known for off-target effects. We’re wondering, too, if the holy light emanating from the hand of a CRISPR-ing God is meant to imply that She is among those researchers interested in combining CRISPR with optogenetics?
Most damningly, though, this metaphor does nothing to explain how CRISPR actually works.
A bomb removal squad
CRISPR, the disruptor http://t.co/6U9M4V2E9h pic.twitter.com/Uwo5JWFj72
— Nature News&Comment (@NatureNews) September 15, 2015
The framing of CRISPR as a method to remove ticking time bombs lurking within our DNA is true enough: Researchers do want to use the technology to take out genetic mutations that cause deadly diseases.
But this visual metaphor confuses the biology. The destructive power in DNA lies in the base pairs themselves, not in between them, where this red canister is placed. And again, this does nothing to shine light on CRISPR’s mechanism of action.
A handyman at work
Can CRISPR–Cas9 boost intelligence? https://t.co/SetEfPfDZr pic.twitter.com/fLUfBXbAV7
— Scientific American (@sciam) September 26, 2016
We had high hopes for this analogy, which came courtesy of the National Institutes of Health. But alas, it mostly disappoints.
The idea, as we understand it, is that CRISPR-Cas9 acts to modify precisely the correct segments of DNA, similar to how a handyman uses a particular wrench to loosen or tighten a nut or bolt of a specific size and shape.
But we’re scratching our heads to come up with a real-life construction scenario where what’s visualized here would actually happen. We get the sense that someone in pursuit of a fresh analogy came up with this one only after concluding that all the good analogies were already taken.
Is genome editing gone be our future? What is genome editing? via @yourgenome https://t.co/Z5rPa1PtH8 #genetictesting #newlifegenetics
— NewLifeGenetics (@NewLifeGenetics) October 25, 2017
This analogy is so 2012. Sure, an eraser is a fine way to think about CRISPR’s powers to delete. But that only goes halfway — what about CRISPR’s powers to add or replace? And it loses the physicality of CRISPR-Cas9’s cutting action for no good reason. (In the interests of full disclosure, we must admit that STAT has used this one in the past. Apologies.)
A surgeon’s scalpel
Scientists in the UK could win approval to genetically modify human embryos https://t.co/H7MYE2HM3E #news pic.twitter.com/VXPjH6ex93
— Olaoye Somide (@kamparia) January 14, 2016
The notion of CRISPR as a surgeon’s scalpel nicely captures its cutting action. But points are deducted for the suggestion that CRISPR is as precise as a surgeon’s tool must be.
A pair of scissors
Genetic Architects Untwist DNA’s Turns https://t.co/79cks6XLl1 pic.twitter.com/cG91aFGMFI
— TeselaGen Biotech (@TeselaGen) July 24, 2017
We like the simple explanatory power of a plain-old pair of scissors to describe CRISPR-Cas9’s cutting action. It’s better than the scalpel metaphor at conveying the technology is a blunt instrument. But points are deducted for not addressing CRISPR’s powers to add or replace.
‘Search and replace’ in Microsoft Word
So cool to wrap up #AtlanticPulse w/ convo on gene editing. "Think of CRISPR as like a search & replace function in Microsoft Word" –@zhangf pic.twitter.com/9YFnbel90b
— Jocelyn M. Zeitzoff (@jocemiller) June 13, 2017
This analogy comes by way of the authority: Feng Zheng, the groundbreaking Massachusetts Institute of Technology scientist who helped create CRISPR-Cas9.
Zheng’s comparison is a good one overall — especially when he explains how it works with the song “Twinkle Twinkle Little Star.” But it’s still an imperfect one, because it implies greater precision than CRISPR actually allows.
To continue the analogy: If you use CRISPR to search for “the” and replace it with “this,” it would work as intended sometimes. But because CRISPR sometimes finds something it shouldn’t, you might also wind up with jumbled words describing the study of the divine as thisology and a book of synonyms as a thissaurus.
CRISPR: “Sort of like organic matter Photoshop” is definitely the best analogy i’ve heard https://t.co/dcZykGx5gd via @Jezebel
— Jon Salm (@salm) February 16, 2017
We really like this comparison, exemplified by writer Aimée Lutkin’s turn of phrase describing CRISPR as “sort of like organic matter Photoshop.”
To be sure, you’re not literally cutting anything, as CRISPR-Cas9 does, when you use the Adobe image editing software. But we saw explanatory power in the fact that Photoshop lets you make zoomed-in changes, down to the level of a single pixel — just as CRISPR can make changes at the level of the As, Ts, Cs, and Gs that make up the genetic code.
And as anyone who’s been victim of a bad Photoshop job knows, there’s plenty of room for the tool to go awry.
A Swiss Army knife
#CRISPR/Cas9: a molecular Swiss army knife of multiple genetic modifications in S. #cerevisiae http://t.co/QlBDRJWlyX pic.twitter.com/5Prg9WsFnU
— FEMS (@FEMSTweets) March 20, 2015
Folks, we have a winner: A Swiss Army knife is the best analogy we found for what CRISPR can and can’t do.
Like the other cutting instruments on our list, a Swiss Army knife gets points as a good visual because CRISPR-Cas9 literally cuts DNA. But a Swiss Army knife breaks out of the pack because it has different blades for different tasks — comparable to CRISPR’s ability to cut something out, introduce a single one-letter change, or make an insertion without a deletion. Swiss Army knives also strike the right middle ground between a precise cut and a blunt cut, a good way to think about CRISPR’s capabilities.
And if that’s not enough: Both CRISPR and Swiss Army knives have recently been at the center of heated legal fights over intellectual property.