Context for my Nature piece on redefining “gene edit” to be more precise

CRISPR gene edit vs mutation
CRISPR gene edit vs mutation. Analogy to editing a book with a scalpel. Photo Paul Knoepfler

When I say “gene edit” or “genome editing”, what’s the first thing that pops in your mind?

CRISPR gene edit vs mutation
CRISPR gene edit vs mutation. Analogy to editing a book with a scalpel. Photo Paul Knoepfler

It will depend on who you are.

For many lay people until a few weeks ago when the world heard about He Jiankui‘s claim of CRISPR’d babies they may not have had anything pop in their heads when hearing “gene editing.” Now perhaps they think of babies bearing specific genetic changes.

I bet most of them who think that way today are envisioning that He made very precise, deliberate changes in the genomes of those twin girls. Really He didn’t. He made what are called random “indels” in the CCR5 gene, which are random insertions or deletions of DNA by cells after introducing of CRISPR. You can read more about why I think He didn’t really gene edit those girls, but instead mutated them here.

When scientists hear or read the largely synonymous phrases “gene editing” or “genome editing” we also have different things invoked in our minds depending on each one’s experience and view of the bigger picture. My view of gene editing has changed to be more narrow over the last year or two such that I think the term should be reserved for precise, deliberate changes and random indels (even if made in the target gene of interest) should be excluded.

I articulated this view in a Nature correspondence piece that came out today.

I feel like some context for this piece is required. Unfortunately, these kinds of correspondence pieces are required to be super short. When I originally wrote the first few drafts, there was much more to it that later got edited out. For instance, precise, intentional indels in my view should still be called “gene editing.”

Also, I never saw the final title and I don’t really like it, particularly the word “sloppy,” which seems provocative. Authors of these pieces don’t get to choose the titles.

Importantly, I’m not claiming some kind of unique authority on what the term “gene editing” should mean, but rather I’m expressing one, strong opinion. Others that I greatly respect including Fyodor Urnov (a pioneer and authority on gene editing) disagree and are arguing just as strongly that I’m wrong. I respect that. He and others have a point that some key work in the past including clinical efforts have already used the phrase gene editing or genome editing so if we change the meaning now, isn’t that problematic? Shouldn’t we be realistic about this?

Maybe so, but in science I’d say we have to be open to things evolving.

I myself have used the phrase “gene editing” in a very broad way in the past that was inclusive of random indels, but as I said again my view of the term has evolved over time to be less inclusive of various types of changes. Part of what got my thinking about “gene editing” in a different way were discussions with colleagues here at UC Davis including especially with bioethicist Mark Yarborough.  He and others here at UCD coauthored a piece in 2015 on the metaphor of gene editing and genetic change, which is worth a read. However, a larger motivation for me to view gene editing differently was just a straightforward desire as a scientist for more precision in terminology. As alluded to earlier in this post, I’m also concerned that the public isn’t thinking of “gene edits” to include fairly random DNA changes.

Still others have pointed out that various alternatives to “gene editing” including “mutation” and “genetic modification” might raise concerns in some of the public if meant in the human context. Potential patients or clinical trial participants might get concerned too. Maybe so, but if this language is more accurate, should we pick the more politically correct, but I would say less accurate term “gene editing” instead anyway?

I hope this is just the start of a healthy debate on how we think and talk about gene editing.

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