The Cuttlefish Is a Master of Disguise. Tessa Montague Wants to Get Inside Its Head.

As a teenager, Tessa Montague earned a black belt in kickboxing. “I thought that was the secret to a successful career as a spy,” she said. But it was science, rather than spy craft, that ultimately seized her imagination. During a summer internship at London’s National Institute for Medical Research, she studied limb formation in chick embryos. The project landed her a spot at the Intel international science fair, launching her career as a scientist. “I loved the freedom, and the possibility of discovering something about the biological world that no one else knew,” she said.

As a graduate student at Harvard University, she co-developed a free web tool, CHOPCHOP, that lets scientists tinker with the genetic code of viruses and animals using the CRISPR gene-editor. CHOPCHOP has since been used to edit hundreds of organisms, from viruses to butterflies to pigs, to study the brain and more. While finishing her PhD at Harvard, Montague took a six-week course at the Marine Biological Laboratory in Woods Hole, Mass. She was in search of an unusual animal for studying the brain. Not a well-studied model organism like a fruit fly or mouse, but a lesser-known animal with some type of intellectual superpower.

After a 10-minute talk on cephalopods, she was hooked. “Within 60 seconds, my whole life flashed before me,” she said. “This is it!”

What about cuttlefish grabbed you?

They’re mollusks, so they’re most closely related to clams and snails. Yet they have the largest brains of all the invertebrates. They can do problem solving, learning, and memory. They have three hearts, blue blood, and can regenerate their arms. But what’s truly most amazing is their ability to camouflage within milliseconds by changing both the color and the texture of their skin. Color change is controlled by the brain!

This has not been an easy undertaking. You’ve had to learn how to breed cuttlefish and develop unique experiments to study their intelligence. Why go to all this effort?

During my PhD I attended a lot of seminars, and there was a theme to my favorite talks: they were given by scientists who were asking big questions in new model organisms, such as aging in killifish, navigation in bats, and the origin of multicellularity in choanoflagellates. I decided that if I could ask a big question by studying an unusual creature, I could carve out a niche for my career, have greater freedom, and be more creative. When I discovered cephalopods, specifically cuttlefish, and realized they had so many fascinating behaviors and you could breed them in the lab, I knew this was it.

How’d you convince Richard Axel, a Nobel Prize winner, to let you set up your own cuttlefish facility as a postdoc?

I reached out to him by email and when he agreed to interview me, I honestly thought he was just humoring me. I explained why I believe an animal that uses its brain to camouflage is so profound: the cuttlefish looks at its surroundings, creates an internal representation of that scene in the brain, and then recreates an approximation of what it’s seen on its skin. The animal shows you what it’s thinking on its skin! I think he connected with the idea because he’s interested in how the brain creates internal representations of the olfactory world. My main job was to persuade him that studying the brains of cuttlefish was doable, because we can breed them in the lab, collect embryos, and potentially inject them to make transgenic cuttlefish. Still, I don’t really know why he agreed to it. I guess he’s a little crazy like I am.

What’s the most surprising thing you’ve learned so far?

The cuttlefish surprise me all the time. We once set up a camera to film one over the weekend, and on Monday, watched the footage. For most of the video the cuttlefish just swam around or camouflaged on a rock. But on a few occasions, when it seemed to be asleep, it suddenly flashed a series of dramatic patterns, with waves of yellow, black, and white, and suddenly became spiky and then smooth. It was almost like a dream. Intriguingly, the cuttlefish produced the exact sequence of patterns a few hours later. I don’t know what it means, but I learned that the cuttlefish still has many secrets to unveil. 

What kinds of behaviors have you observed in the lab?

We recently built a coral reef display tank to replicate their natural habitat in the Philippines (with a live webcam), and that has triggered many intriguing social patterns. We can see the moment two males become aggressive with each other because they flare into a stereotyped black and white pattern, and they stretch and curve their bodies towards each other. Likewise, they make amazing waves across their skin when they seem to be alert or hunting. I love watching them and trying to decipher their skin patterns. Their mating behavior is also fascinating. When a male and female mate, the female stores the sperm in her cheeks and can use it weeks later. This supposedly allows her to choose which males she wants to fertilize her eggs.

What’s the ultimate goal of this work?

My goal is to use cuttlefish camouflage to understand how the physical properties of the visual world are represented by patterns of neural activity in the brain, and how this representation is transformed into an approximation of the physical world on the skin. My hope is this work will reveal some fundamental principles about how brains function. Humans are the only animals that can say what they’re thinking and feeling. But cuttlefish are unique in that they represent both their emotional state and the world around them using patterns on their skin. The ability to understand the neural basis of emotion and perception in cuttlefish could provide insight into human cognition, in both its functioning and impaired form. 

To uncover the neural basis of camouflage and emotion in cuttlefish, we need to develop a series of tools: an understanding of its developmental stages, a map of its brain. We also need more sophisticated tools, like transgenic animals whose neurons light up when they’re active, and optogenetic tools that allow us to control the cuttlefish’s neurons. If we learn enough about its brain, we could use optogenetics to control the pattern the cuttlefish displays on its skin or prompt it to flare in a dramatic display of aggression. We’re also trying to develop behavioral tools like a virtual reality environment in which we trigger camouflage behavior to carefully crafted stimuli.

How do you get past those frustrating days when nothing goes right?

The project has so many different arms (behavior, molecular biology, developmental biology, computation) that when one thing isn’t working, there are usually breakthroughs in other areas. When we have setbacks, I just remind myself how far we’ve already come. When we first built our facility, we had just two animals, Posh and Becks. They wouldn’t eat any food, change color, or do any normal social behaviors. We couldn’t figure out why. Eventually we discovered that they couldn’t bear being in a white tank. As soon as we moved them to a glass tank, they ate immediately and dissolved into the shadows. We now have a busy facility of more than 200 healthy cuttlefish, who are constantly dazzling us with new and unexpected behaviors. When I need some inspiration, I just sit in front of our coral reef tank and watch the cuttlefish as they swim up to the glass. We look into each other’s eyes, and I try to imagine what they’re thinking.