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How — and why — scientists created a see-through squid

ARI SHAPIRO, HOST:

For most of us, it would take magic to become invisible, but for some lucky, tiny squid, all it took was a little genetic tweaking. As part of our Weekly Dose of Wonder series, NPR's Jon Hamilton explains how scientists created a see-through squid.

JON HAMILTON, BYLINE: The squid come from the Marine Biological Laboratory in Woods Hole, Mass. Josh Rosenthal is a senior scientist there. He says even the animal's caretakers can't keep track of them.

JOSH ROSENTHAL: They're really hard to spot. We know we put it in this aquarium, but they might look for a half-hour before they can actually see it. They're that transparent.

HAMILTON: Almost invisible. Carrie Albertin, a fellow at the lab, says studying these creatures has been transformative.

CARRIE ALBERTIN: They are so strikingly see-through. It changes the way you interpret what's going on in this animal, being able to see completely through the body.

HAMILTON: Scientists can watch the squid's three hearts beating in synchrony or see its brain cells at work. And it's all thanks to a gene-editing technology called CRISPR. A few years ago, Rosenthal and Albertin decided they could use CRISPR to create a special octopus or squid for research.

ROSENTHAL: Carrie and I are highly biased. We both love cephalopods - right? - and we have for our entire careers.

HAMILTON: So they focused on the hummingbird bobtail squid. It's smaller than a thumb and shaped like a dumpling. Like other cephalopods, it has a relatively large and sophisticated brain. Rosenthal takes me to an aquarium to show me what the squid looks like before its genes are altered.

ROSENTHAL: Here is our hummingbird bobtail squid. You can see him right there in the bottom, just kind of sitting there hunkered down in the sand. At night, it'll come out and hunt and be much more mobile.

HAMILTON: At the moment, the squid is camouflaged to blend in with the sand. That's possible because of organs in its skin called chromatophores. They contain pigment that can be manipulated to change the squid's appearance. The scientists wanted to create a bobtail squid without any pigment, and Albertin says she and Rosenthal knew that in other squid, pigment relies on a gene called TDO.

ALBERTIN: We said this is an obvious first target. And we went, and we tried to knock out TDO, and nothing happened.

ROSENTHAL: So we said, OK, what could have gone wrong?

HAMILTON: Albertin says it turned out that these squid have a second gene that also affects pigment.

ALBERTIN: We were able to identify that gene, and when we targeted both of them, lo and behold, we were able to get albinos.

HAMILTON: And because squid have clear blood, thin skin and no bones, the albinos are all but transparent. These days, there's a whole room in the lab devoted to creating see-through squid. Albertin takes me to a technician who's working on an embryo smaller than a BB pellet.

ALBERTIN: And so you can see under the microscope, we use pairs of forceps to tear away the jelly layers.

HAMILTON: Next, the technician will use a quartz needle to inject genetic material that will delete the pigment genes and create a transparent squid. Albertin and Rosenthal knew that these animals would be of interest to brain scientists, so they called Ivan Soltesz at Stanford and Cris Niell at the University of Oregon.

ROSENTHAL: We said, hey, you guys. We have this incredible animal. Want to look at its brain? And they jumped on it.

HAMILTON: Soltesz and Niell inserted a fluorescent dye into the animal's brains. The dye glows when it's near brain cells that are active. Then the scientists projected images onto a screen in front of the squid, and Albertin says brain areas involved in vision began to glow.

ALBERTIN: The evidence that they were able to actually get from this and look at activity in an unperturbed squid made all of us just kind of jump through our skins. It was really exciting.

HAMILTON: Because it suggests that her see-through squid will help scientists understand not only cephalopods, but all living creatures. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.

NPR transcripts are created on a rush deadline by an NPR contractor. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.

Jon Hamilton is a correspondent for NPR's Science Desk. Currently he focuses on neuroscience and health risks.