September 26, 2020

The Niche

Knoepfler lab stem cell blog

He Jiankui didn’t really gene edit those girls; he mutated them

Did Chinese researcher He Jiankui really CRISPR gene edit the CCR5 gene in two embryos producing twin baby girls? In my opinion the answer is “no”, but probably not for the reason you might think at first.

He proclaims gene edits

He claimed he had made twin baby girls with “gene edits”, which I feel is unethical overall and risky to those babies. He’s announcement also may have been intentionally timed to occur right before an international meeting on human gene (or genome) editing last week too. Glossy YouTube videos from He accompanied all of this as well, raising further suspicions of a PR angle for himself. For these and other reasons, I believe we need a temporary 3-year pause on implantation of CRISPR’d human embryos.

Could He have been stopped and when?

CRISPR gene edit vs mutation
CRISPR gene edit vs mutation. Analogy of what He did to trying to edit a book with a thrown scalpel. Photo Paul Knoepfler

Given the timing and He’s actions, the organizers of the human genome editing meeting could have yanked He’s invitation to speak, but they didn’t. On the whole, that was probably a wise decision so we could all learn more about what supposedly happened.

Others argued He shouldn’t have been allowed to retain that meeting platform since what he did appeared to most likely be unethical on a number of levels. Beyond the questionable science of He’s work, there are still unresolved ethics and transparency questions. As my colleague here at UC Davis Mark Yarborough wrote, in a sense ideally the life sciences community should have hoped to have stopped He much earlier in a different kind of way including via better bioethics training and a different kind of research culture.

Did He really “gene edit” them?

Some people have wondered if the whole thing might be a fraud in which He didn’t actually make CRISPR’d babies. Based on what we do know, I think most likely He isn’t lying at a core level about having made babies with CRISPR, although we may never know for sure. However, at a common sense level I would still say that He did not gene edit these babies.

What do I mean?

As someone who has been doing genetics for a long time, mostly in mice, I remember that in the pre-CRISPR era we called various interventions in genes by other terms: mutations, genetic modifications, gene targeting, etc. Some of us still often use those terms. “Gene editing” sounds more precise and deliberate and benign. Maybe that’s the appeal of this term to some.

In my view as a scientist who uses CRISPR, not all uses of it actually qualify as gene editing and it’s not just semantics. I would argue the term “gene editing” should be reserved only for precise, deliberate changes that justify using versions of the key word “edit”. There’s been far too much loose use of the phrase ‘gene editing” and others like “gene surgery.” This kind of language can be harmful by misinforming people, exaggerating precision, and underestimating risks.

How we write and talk about science is very important (see more on CRISPR metaphors here, work also led by Mark Yarborough). If you think about the “edit” analogy more broadly, would you want your editor to just throw a scalpel or scissors at a specific section of your writing (even if for some weird reason this editor is a very accurate although not perfect thrower) and hope for the best outcome? I’d hardly call that editing.

Gene editing versus mutating

To qualify as a gene edit, He would have had to have been deliberately trying to make one and only one precise change, and have achieved that edit alone. That’s not at all what happened. Instead, it seems He deleted fairly random chunks of a certain region of CCR5 in the human embryos who supposedly became twin girls. None of the He mutations were the same as those occurring naturally in humans who then have substantial resistance to HIV infection.

Even in basic science research using CRISPR, if we make random mutations (what are collectively termed indels, which is short for “Insertions” and “deletions”) should we be calling that “gene editing”? No, we really shouldn’t, even if sometimes those indels are useful and powerful tools. In my lab we have used CRISPR to both make precise gene edits and separately to make indel mutations.

A gene edit is still a type of mutation, but a uniquely precise, deliberate one, while conversely not all mutations are gene edits. Further, not everything done by CRISPR should be called “gene editing.”

Frankly, what He did really was to mutate those twin girls, particularly since he was changing a normal wildtype gene to a mutant form. We should call it what it is so as to be as accurate as possible and think about the reality of the situation.

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