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RISPR-Cas9 is complicated.

Thats 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, weve 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 STATs 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.

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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:

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 CRISPRs precision. It also suggests, wrongly, that CRISPRs 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 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 foroff-target effects. Were 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.

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 CRISPRs mechanism of action.

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 were scratching our heads to come up with a real-life construction scenario where whats 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.

This analogy is so 2012. Sure, an eraser is a fine way to think about CRISPRs powers to delete. But that only goes halfway what about CRISPRs powers to add or replace? And it loses the physicality of CRISPR-Cas9s 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.)

The notion of CRISPR as a surgeons scalpel nicely captures its cutting action. But points are deducted for the suggestion that CRISPR is as precise as a surgeons tool must be.

We like the simple explanatory power of a plain-old pair of scissors to describe CRISPR-Cas9s cutting action. Its better than the scalpel metaphor at conveying the technology isablunt instrument. But points are deducted for not addressing CRISPRs powers to add or replace.

This analogy comes by way ofthe authority:Feng Zheng, the groundbreaking Massachusetts Institute of Technology scientist who helped create CRISPR-Cas9.

Zhengs comparison is a good one overall especially when he explains how it works with the song Twinkle Twinkle Little Star. But its 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 shouldnt, you might also wind up with jumbled words describing the study of the divine as thisology and a book of synonyms as athissaurus.

We really like this comparison, exemplified bywriter Aime Lutkins turn of phrase describing CRISPR assort of like organic matter Photoshop.

To be sure, youre 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 whos been victim of a bad Photoshop job knows, theres plenty of room for the tool to go awry.

Folks, we have a winner: A Swiss Army knife is the best analogy we found for what CRISPR can and cant 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 CRISPRs 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 CRISPRs capabilities.

And if thats not enough: Both CRISPR and Swiss Army knives have recently been at the center of heated legalfights over intellectual property.

Business Reporter

Rebecca covers the business of biopharma.

Originally posted here:
The best and worst analogies for CRISPR, ranked

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