What The First Genetically Modified Squid Means for Science : Short Wave The first genetically altered squid is here. NPR's Nell Greenfieldboyce explains how this breakthrough was made and why it's a game changer for scientists who study these critters.
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Gene-Altered Squid Could Be The Next Lab Rats

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Gene-Altered Squid Could Be The Next Lab Rats

Gene-Altered Squid Could Be The Next Lab Rats

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  • <iframe src="https://www.npr.org/player/embed/900886442/901128815" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
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MADDIE SOFIA, BYLINE: You're listening to SHORT WAVE...

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SOFIA: ...From NPR.

EMILY KWONG, HOST:

Hey, everybody. SHORT WAVE reporter Emily Kwong here with NPR science correspondent Nell Greenfieldboyce.

NELL GREENFIELDBOYCE, BYLINE: Hey, Emily.

KWONG: Hey. So we're going to talk about a very special list of creatures today that includes worms, fruit flies, mice and my favorite, zebrafish - model organisms.

GREENFIELDBOYCE: They are model organisms. So most laboratory biology is done on just a few organisms - so-called model organisms. And, you know, they are, you know, what most of our understanding of biology comes from - experiments with just these few, few critters.

KWONG: I'm wondering now, why is it just a few?

GREENFIELDBOYCE: Well, you know, some of it's practical. So, you know, they're easy to keep in the laboratory. They reproduce quickly. It's easy to take care of them.

KWONG: Yeah.

GREENFIELDBOYCE: But most importantly, scientists over the years have worked out how to routinely alter their genes, and this can produce all kinds of insights into what that gene does for things like behavior or diseases or possible treatments, and all of that can sort of potentially be applied to our understanding of humans.

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JOSH ROSENTHAL: With these organisms, you could understand what genes did by manipulating them. And that really became an indispensable part of biology.

GREENFIELDBOYCE: OK, that's Josh Rosenthal. He's a biologist at the Marine Biological Laboratory in Woods Hole, Mass. And he's one of the scientists I spoke to when I went to visit the lab last year. This was sort of pre-pandemic, when I could just, like, go out and see a lab pretty easily.

KWONG: Yeah, the before times. I miss that. OK, so model organisms - they're helpful to science because we understand their genetic makeup, and scientists can modify their genes to figure out kind of what happens on a granular level with them, right?

GREENFIELDBOYCE: Yeah, yeah. So you can see how that's useful.

KWONG: Yeah.

GREENFIELDBOYCE: But there is a dark side. Josh told me there are drawbacks to focusing on just a few creatures.

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ROSENTHAL: We're really missing out on, I would say, the diversity of biology solutions to problems.

GREENFIELDBOYCE: So what he's saying there is it's a big world out there with all kinds of organisms whose genes we could be studying, but, you know, we're not really. So Josh and his colleagues have been trying to add another organism to that short list of model organisms, and what he's most interested in are squids.

KWONG: Oh, like cephalopods.

GREENFIELDBOYCE: Right - squid, cuttlefish, octopuses - all cephalopods.

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GREENFIELDBOYCE: Has anyone ever made a genetically altered cephalopod?

ROSENTHAL: Arguably, we have here over the last year, but no one has published this yet, and this is really work in progress.

GREENFIELDBOYCE: So, Emily, guess what just happened.

KWONG: They published.

GREENFIELDBOYCE: They published - you got it. Their study recently came out in the journal Current Biology. And if you're a biologist interested in weird new critters, it's a game-changer in terms of being able to study things you weren't able to study before.

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KWONG: So today on the show, genetically modified squid. But don't worry; it's not the kraken. We visit a lab full of cephalopods to talk about this breakthrough in the world of squid science.

OK, Nell Greenfieldboyce, last year you visited the Marine Biological Laboratory in Woods Hole, Mass. Tell me about it. What was it like?

GREENFIELDBOYCE: So it's this, you know, sort of beautiful location right there on the coast of Massachusetts.

KWONG: Yeah.

GREENFIELDBOYCE: And, you know, you go inside, and, you know, they took me to this room full of kind of burbling aquariums everywhere. And...

BRET GRASSE: This is where we hold all of our exotic animals.

GREENFIELDBOYCE: The guy giving me the tour was Bret Grasse, and his official title there is manager of cephalopod operations.

KWONG: Amazing title.

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GRASSE: So we've got our beautiful, flamboyant cuttlefish. We've got our striped pyjama squids. These ones are native to Australia. We've got our Octopus chierchiae, which is the pygmy zebra octopus. They're native to Nicaragua - a very small octopus species that doesn't get much larger than a table grape.

KWONG: A table grape, nice.

GREENFIELDBOYCE: Yeah. So they're looking at all kinds of squid and octopuses to try to find ones that, you know, are easy to take care of, that reproduce quickly, that are just going to be good to be sort of like the next lab rat. And their work involves everything from the very latest high-tech kind of, like, gene-editing tools to just, like, a bucket of rocks sitting on the floor.

KWONG: Why rocks?

GREENFIELDBOYCE: Well, you know, they use them to make, like, little habitats in the tanks, but they also use them to weigh down some of the lids.

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GRASSE: So, you know, octopuses are notorious for being able to kind of escape out of their enclosures.

KWONG: I've heard of this - that in aquariums, octopuses have been known to climb out and wander around.

GREENFIELDBOYCE: Yeah, they're clever. You know, so when I visited, Bret told me there were roughly around 3,000 cephalopods under their care there. But honestly, walking around and looking in the tanks, you can hardly see any because they like to hide in those rocks and, you know, other little things, little containers that the keepers put in their tanks. At one point, Bret opened up this one plastic container and reached into the water and pulled out this little, like - like a terracotta pot. And inside was this California two-spot octopus.

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GRASSE: She is right down in there. You can kind of see her eyeball checking us out.

GREENFIELDBOYCE: I can barely see her, yeah.

GRASSE: Yeah. And so basically, this is a - kind of a common den. Either they're going to find rocks or some sort of basically dark enclosure.

GREENFIELDBOYCE: So this was a female octopus sitting on her eggs. And while we were looking at her, she sort of shot out some water at us.

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GRASSE: You see she's kind of trying to squirt some water here. She either thinks that I'm going to give some food, or she's just trying to say, you know, I'm sitting in here, taking care of my eggs and, you know, come back another time, so.

KWONG: Nell, if you had a podcast called Nell Spies An Octopus, I would listen to it.

GREENFIELDBOYCE: Well, we would have a lot to talk about because cephalopods are pretty crazy. I mean, they have these sophisticated brains. They can solve puzzles. They can change their skin color, like, in an instant. They can regrow arms. They travel using jet propulsion. I mean, some people have said they are as close to aliens living on Earth as we've got.

KWONG: That is so cool. Honestly, we should do a whole episode just about cephalopods. But I want to go back to this research question about using them as model organisms. So why cephalopods in particular?

GREENFIELDBOYCE: Well, it's all those odd features that makes them interesting to biologists. I mean, for example, I mentioned their brains. You know, they're clearly sophisticated problem-solvers, but their brains just look completely different from our own. Like, they showed me one in a glass vial that looked almost like a triangle shape. And, you know, there's other brains that look like doughnuts that wrap around the esophagus, you know?

At the same time, we know that some of their brain chemistry has got to be somewhat similar to ours 'cause there have been experiments looking at how octopuses react to the drug ecstasy, right? Like, it seems to make them, like, a little more friendly and cuddly, too.

So, you know, it's just fascinating to look at these creatures that are, on the one hand, so different and, on the one hand, similar, and studying them could help scientists see what's necessary and what's not for being able to, you know, perform, you know, amazing mental feats like the ones people can do and, apparently, you know, some cephalopods seem capable of.

KWONG: Gotcha, gotcha. OK, and that brings us to today.

GREENFIELDBOYCE: Right. So it was a little bit of a process for the scientists to build gene-modification tools for cephalopods. And they actually first used a squid that lives in the waters around Woods Hole.

KWONG: OK.

GREENFIELDBOYCE: And one member of the research team, Karen Crawford, had already figured out how to fertilize its eggs in the lab. And so what the team did is sort of try to figure out how they could inject kind of gene-altering materials. And Josh Rosenthal, that biologist from the beginning, he told me it just wasn't easy at all because the fertilized egg is surrounded by this, like, rubbery, tough coating. He said it was almost like a Super Ball kind of thing.

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ROSENTHAL: For months, we would have needles break. We couldn't figure out how to get in.

And so we sort of - we came up with a way to get the injection needle in finally, and that turned out to be one of the biggest roadblocks in this study.

GREENFIELDBOYCE: But they finally did it, and the gene they messed with is a pigmentation gene. So normally, these squid have small dark spots on their skin. And with this injection of gene-altering materials, the team was able to mostly turn off that pigmentation gene in baby squid. And so as the squid grew, those spots just mostly weren't there.

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ROSENTHAL: Pigment genes are easy 'cause you can see them, right? You can see if it's working as the things develop.

KWONG: Oh, so they were able to see right away that it was successful because they made these gene-altered squid with fewer spots.

GREENFIELDBOYCE: Yeah. I talked with Carrie Albertin. She's a member of the research team. And she told me for her, this is just a huge deal.

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CARRIE ALBERTIN: This is something that, honestly, if you asked me five years ago if we'd be able to do, I would've just giggled and said, I'd dream of it. But, you know, I didn't think it would be possible, and yet here we are.

GREENFIELDBOYCE: Yeah, and she's not the only person who's pretty thrilled about this. I called up squid biologist Sarah McAnulty. She's affiliated with the University of Connecticut.

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SARAH MCANULTY: This is, like, a huge advancement for cephalopod researchers all over the world. We should all be popping bottles of Champagne. This is amazing.

KWONG: I can only imagine the party that would happen with squid scientists over this. OK, so when all the Champagne is drunk, what is next for these scientists now?

GREENFIELDBOYCE: Well, this particular squid species isn't really amendable to being raised to maturity in the lab. It just gets sort of too big.

KWONG: OK.

GREENFIELDBOYCE: But there are plenty of other smaller squid and octopus species, like the ones they've been trying to raise in all those tanks. And the team is basically working to transfer the same kind of technology to the ones they're cultivating in captivity.

KWONG: OK.

GREENFIELDBOYCE: And, you know, what they want to do next is, you know, add in genes or alter the function of existing genes rather than just, like, knocking out and sort of blocking existing ones from doing their job.

KWONG: OK, Nell, I got to ask one more question that's been nagging at me during this whole conversation. If squid are going to maybe be the next lab rat, you said, what are the rules around working with them as a model organism?

GREENFIELDBOYCE: So that's interesting. In the U.S., Josh told me that the sort of typical animal welfare rules don't apply to invertebrates. They don't apply to animals without backbones. I mean, you know, most institutions have, like, Animal Care and Use committees that make sure that animals are being treated humanely. But at the Marine Biological Laboratory, even though it's not maybe legally required, they've been really careful about that, and they take the ethical issues really seriously.

ROSENTHAL: And so we've tried to be quite preemptive on this, in putting together what I think is in the U.S. a one-of-a-kind policy for cephalopod research.

GREENFIELDBOYCE: So they're pioneering, you know, efforts to figure out, for example, what anesthesias are useful for cephalopods, if the animals need to be sacrificed for the research. And they're trying to understand how to keep them in living conditions that are stress-free for the animals.

KWONG: OK. Well, we'll see what the future holds for cephalopods in the laboratory. Thank you so much, Nell Greenfieldboyce, for coming on the show.

GREENFIELDBOYCE: Thank you.

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KWONG: Today's episode was produced and fact-checked by Yowei Shaw and edited by Viet Le. I'm Emily Kwong, filling in for Maddie for the next few days. You're listening to SHORT WAVE, the daily science podcast from NPR.

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