What’s the Future of Gene Editing?

One of the most surprising and remarkable discoveries in recent scientific history has been CRISPR. Short for Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR is a form of immune system that evolved in bacteria more than a billion years ago to defend against persistent viral threats. Under attack, bacteria can snip a small fragment of a virus’s DNA, store it in the CRISPR region of their genome, and then use it to recognize and destroy the same virus if it returns. The CRISPR-Cas9 system, to give it its longer name, consists of a short strand of guide RNA that identifies where to cut the DNA and a protein that acts as the molecular scissors.

What made this system truly revolutionary was the demonstration in 2012 that it could be reprogrammed with different pieces of guide RNA to edit virtually any genome in any species, and at a level of precision and ease that far surpassed existing gene-editing tools. Since then, the editing capability of CRISPR has been tested on everything from developing disease treatments to engineering drought-resistant crops to resurrecting genes of extinct species. The possibilities have expanded so rapidly that researchers, ethicists, and regulators have found themselves struggling to keep up.

One person acutely aware of the power of CRISPR is Jennifer Doudna , co-developer of the technology. Doudna, who received the Nobel Prize in Chemistry in 2020 with Emmanuelle Charpentier for this pioneering work, has been a prominent voice not only for its vast potential but also for its responsible and ethical use. In this episode of The Joy of Why , Doudna tells co-host Janna Levin how her early, “rebellious,” decision to study RNA led her on a serendipitous path to one of biology’s most transformative discoveries. They also discuss the breakthroughs, barriers, and frontiers that will define CRISPR’s true impact.

Listen on Apple Podcasts , Spotify , TuneIn  or your favorite podcasting app, or you can stream it from Quanta .

Transcript

[ Music plays ]

JANNA LEVIN: Okay, here we go. I’m Janna Levin.

STEVE STROGATZ: And I’m Steve Strogatz.

LEVIN: And this is The Joy of Why .

STROGATZ: A podcast from Quanta Magazine , where we discuss some of the biggest unanswered questions in math and science today.

LEVIN: Hi, Steve. Here we are.

STROGATZ: Hi, Janna. It’s a new season.

LEVIN: I know, this is fun. Season Five. I’m pretty excited to talk to you about CRISPR today. Have we ever had this conversation?

STROGATZ: No, we have not.

LEVIN: Do you remember first learning about the CRISPR mechanism for gene editing?

STROGATZ: Well, I, I have heard of CRISPR, but I barely know anything about it. Should I think of it as some kind of molecular scissors that can do chopping of bacterial DNA by the bacterium itself?

LEVIN: Yeah, gosh, now you’re going to be challenging me, but yes. CRISPR, it’s a mechanism that can chop the DNA and then insert it. So it’s a combination of a cut and a paste.

STROGATZ: Aha!

LEVIN: And, I so distinctly remember hearing someone describe to me that there was a naturally occurring mechanism in bacteria which indicated they could edit their own genome and splice in the DNA of an invading virus, for instance, and store it for later so that it was more effective as an immune system if that same virus attacks.

STROGATZ: It’s a really cool idea in itself. I mean, aside from any applications it might have, I think I remember from high school biology that bacteria don’t have any immune system.

LEVIN: Yeah. I mean, pretty simple organism. I think about this also, if you just imagine its molecules acting as prescribed, right? Just moving around. When you hear it from this perspective, it sounds like a stroke of genius. Yet, there’s really nobody doing the thinking. It’s just molecules responding.

STROGATZ: You know, thank you for saying that. Because it’s so easy when you hear biologists talk about this or that mechanism. It’s good to remember there’s nobody home. This is, this is molecules.

LEVIN: Yeah. It’s just a little bit of positive charge making it move a little bit towards this. It is incredible that through this kind of iterative steps of just very simple application of basically electrical attraction that something this sophisticated could emerge, and is essential to the survival of an organism, and even the definition of an organism. Absolutely fascinating. Of course, this is our history. We come from very simple organisms ultimately all the way back down, and yet we don’t have a CRISPR mechanism.

So, let me tell you about our guest. Jennifer Doudna is a professor of biochemistry, biophysics, and structural biology. She shared the 2020 Nobel Prize for her incredible pioneering work on CRISPR. First time two women have won the Nobel Prize together, I believe, by the way. She’s at UC Berkeley, and she leads the Innovative Genomics Institute and does so much beyond that.

And I’ve been wanting to speak to her for many years because I find th…