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Octopuses’ Crazy DNA Can Tell Us Some Valuable Stuff About Biology Overall

"They’re ‘the road not traveled’ to intelligence."

On a recent grey afternoon, I peered into a tank at Frank Grasso’s wet lab at Brooklyn College in Flatbush. There was a squishy lump of flesh piled into a back corner of the tank, looking at me with one eye. It was an octopus, still unnamed, because it had arrived the day before, express shipped by FedEx. In a second tank, another octopus was hiding so well I couldn't see it at all.

Their recent travel is why they're so shy, Grasso, a comparative psychologist and cognitive neuroscientist, tells me. And why the octopus in front of me looks more like silly putty than an eight-legged creature that Grasso will soon have opening jars and performing other learning tasks. I’m sympathetic—being shipped overnight doesn’t sound like fun—but vaguely disappointed that I won’t be getting more out of my first octopus encounter.


In The Soul of an Octopus, Sy Montgomery writes that she wanted to meet an octopus because they represent “the great mystery of the Other.” Humans diverged from octopuses evolutionarily more than half a billion years ago, and octopuses have been called the closest thing to an alien we’ll see on earth. “Here is an animal that has venom like a snake, a beak like a parrot, and ink like an old-fashioned pen,” Montgomery wrote. “It can weigh as much as a man and stretch as long as a car, yet can pour its baggy, boneless body through an opening the size of an orange. It can change color and shape. It can taste with its skin. Most fascinating of all, I had read that octopuses are smart.”

These smarts, in particular, have captured our imagination. You’ve heard about octopus shenanigans at aquariums worldwide: their daring escapes, their robust personalities, their desire to play, pick favorite humans, and their ability to solve complicated puzzles. In a recent episode of BBC America's Blue Planet II, an octopus fights off a a pyjama shark first by sticking its arms into the shark's gills to suffocate it, then by camouflaging itself under a pile of shells, in what science writer Ed Yong called "“as thrilling a bit of television as exists”.

This is one of the reasons researchers like Grasso study octopuses at all. They’re invertebrates that have remarkably different brains from humans, yet have evolved complex problem-solving skills, learning, and memory.


“The way that I think about is that they’re ‘the road not traveled’ to intelligence,” Grasso tells me. If he can figure out what makes octopuses tick, what in their biology and brains leads to their intelligence, he could find out fundamental truths about what’s necessary for intelligence in all organisms, including humans.

The fascination with octopuses has become widespread and ardent enough lately as to have created a backlash. In a recent piece in Slate, Daniel Engber makes a case against the octopus's elevated stature amongst invertebrates. He says that we’re just enamored by their flashy tricks and project sophisticated personalities onto them. It’s true that we love when octopuses act out. Who wasn’t delighted by Otto the octopus, who learned how to turn off a light shining on his tank by squirting water at it? When Inky the octopus lifted the lid off his own tank, slinked eight feet across the floor, and down a 164-foot-long drainpipe, he became famous.

“Think of all those anecdotes of octopuses’ impish misbehavior—hiding inside of teapots, pushing toys around, taking valves apart and flooding rooms, squirting jets of water at the researchers who try to study them,” Engber writes. “It’s like we’re all a bunch of nerds, and they’re the underwater rebels.”

When I encountered the nameless, grey, immobile blob in front of me, it was before Engber came out with his affront on an animal we all love to marvel at. But I did wonder: what can we really learn about ourselves from this thing?


Octopuses are weird. They have three hearts, a brain that wraps around their esophagus, and copper carries oxygen in their blood, not iron, meaning they bleed blue.

But to talk about their smarts, we must consider their brains. At first glance, octopus brains look similar to ours: they’re bilaterally organized, so they have a right and left side. But that’s actually only about two fifths of the octopus brain. The other three fifths, and the rest of the octopus central nervous system, is distributed through its body, amongst the arms. Each arm can move and act autonomously; Grasso says it’s a bit like if we had a spinal cord running down each arm and leg.

Because their central nervous system is spread out like this, if you were to scoop out large portions of their bilateral brain (which scientists have done), an octopus would still be able to function. It could feed itself, move around, and act almost normally. Octopuses have 500 million neurons in their bodies, not close to the 100 billion that humans have, but still much larger than other invertebrates (dogs have about 500 million neurons too).

Grasso agrees that talking about animal intelligence can be loaded with projections and anthropomorphisms, so he prefers to speak specifically about just what an octopus can do with its strange brain. When Grasso puts a crab into a jar, and drops it into a tank with an octopus, he’s giving the octopus a task that evolution didn’t prepare it for, since there aren’t jars in the natural world for them to unscrew. But octopuses can still open that jar in a matter of minutes. It’s the kind of problem that other animals in the sea could spend a lifetime not getting, he says.


“They can learn arbitrarily complicated things,” he says. “They’re constantly acquiring new behaviors. They’re able to learn how to exploit new food sources that their ancestors didn’t exploit. They’re able to learn complicated manipulation tasks in order to do that. They can be conditioned, like a dog. There’s evidence that they do observational learning, which is a really amazing thing for a solitary animal—to be able to watch another member of that species and acquire a skill just by watching the other animal do that.”

Primates, like humans, are social animals, and there are theories that say our own intelligence came largely from our interactions with each other. But octopuses differ here: They’re totally solitary from birth. “They’ve arrived at this intelligence in a completely different way,” Grasso says. “That goes back to this idea about what intelligence really is. The octopus lineage didn’t evolve intelligence for being able to solve complex social problems.”

Even the way they move requires brainpower. Unlike humans and other animals with endoskeletons or exoskeletons, the octopus is soft-bodied; there are no hard parts to it except for its beak. When they reach out with an arm to grab for something, they can go in any direction. When I reach for an apple, I have a limited number of “degrees of freedom” which are the different configurations I can move my arm, limited by my elbow, wrist and shoulder joint. Octopuses have an infinite number of different ways they could reach that same apple, and figuring out how to maneuver and coordinate not one, but eight, arms in that way puts a demand on the brain, Grasso says.


They also have an impressive camouflage system; their skin is made up of a large number of individual packets of colored oil, or pigments, that have muscles attached to them. If an octopus wants to make a portion of its arm brown, it stretches those muscles. If it wants to be red, it pulls that patch open and makes it red. It can mix colors, and create complex shades and patterns, which can make it virtually disappear against any backdrop.

Grasso thinks that this too could partly explain their powerful brains; they have to control thousands of droplets under neural control. A twist: the octopus is also colorblind. So it’s achieving this masterful camouflage without being able to see color itself. “That’s a deep puzzle,” Frank says. “How can an animal match colors when there’s no evidence that they have the visual pigments that we would expect to produce color vision, like we have in humans?”

We may have overstated the intent or meaning behind an octopus squirting water at a light in an aquarium. But the morphology of their bodies and brains are still deep wells of biological information, and we have more to learn, says Clifton Ragsdale, a systems neuroscientist at The University of Chicago. He's moving the study of the octopus beyond just observing all of their peculiarities: Ragsdale was part of the team that first sequenced the octopus genome in 2015.

“There are lots of studies done in the middle of last century by British neuroscientists who asked brain and behavior questions specifically about octopus,” he says. “They used the methods of the time and that gave us a lot of information. But it didn’t tell us anything about the large-scale circuitry. It told us hardly anything about the microcircuitry of how the brain is organized. That then prevented us from getting insights into, for instance, how the animal processes visual information. Or how is its memory system set up.”


Ragsdale and his collaborators found that the octopus has a large genome, with 2.7 billion base pairs and more that 33,000 protein-encoding genes (human genomes have about 3 billion base pairs, and 20-25,000 genes). The octopus genome is five to six times larger than other invertebrate genomes that have been sequenced, and has about double the number of chromosomes.

Because their genome is so large, Ragsdale says they thought it might have gone through whole genome duplication, when genetic material is doubled to increase genetic diversity and lead to new traits (this has happened twice in ancestral vertebrates). But they didn’t find any signs of gene duplication, instead seeing that the genome was so large because of the expansion of a few gene families, reordering of other genes, and the appearance of brand new genes.

The gene expansion they were surprised and intrigued by, Ragsdale says, was in the protocadherins, which are genes that regulate neuronal development and interactions between nearby neurons. They saw 168 protocadherin genes in the octopus genome, which is ten times more than other invertebrates and twice as many as mammals. Ragsdale says that it was previously thought that only vertebrates could have this many diverse protocadherin genes.

Their genomes were scrambled too, with genes that are usually found close together on chromosomes nowhere near each other, “like it’s been put into a blender and mixed,” lab member Caroline Albertin said in a statement. Their genomes are highly populated in transposons, or “jumping genes,” which can rearrange themselves on the genome. Ragsdale and his collaborators aren’t sure exactly what their roles are, but they noted there was elevated transposon expression in neural tissues.


Last year, researchers from Tel Aviv University found that octopuses extensively use RNA editing, which means they can alter the expression of their own genes without needing the actual DNA sequence to be changed. In season two of Jessica Jones (spoiler alert) this trait was alluded to: Jessica Jones allegedly got her super powers through genetic editing using octopus DNA. (Octopuses use RNA for their own kind of super powers, like manipulating their nerve cells to adjust to extreme temperature changes.) Since it aired, public interest has been piqued in "octopus DNA."

Ragsdale’s lab has also started to work on octopus arm regeneration. If you amputate an arm, he says, it will grow back and be able to function reasonably well. But an octopus arm isn’t just an arm, it’s a complex camouflage system. Its suckers, which don’t just move but sense and taste, are an extension of its central nervous system.

Humans, on the other hand, don’t regenerate at all. “A night of heavy drinking, yes, you regenerate your liver,” Ragsdale says. “But that doesn’t have a complex three-dimensional structure. We are not going to get any insight into possible mechanisms or therapeutics for that kind of structural regeneration by studying humans and more broadly, studying anything that looks like mammalian regeneration. We have to look elsewhere in the animal world.”

He says that because of the nature of octopus regeneration, it could be applied to spinal cord injuries or damage, where it would be helpful to know how they regrow part of their central nervous system. Using octopus DNA for our own gene editing probably won't be happening any time soon, but it's an example of why he thinks the molecular approach is so useful: we can start picking apart the genome to see how exactly octopuses do the things they do, rather than just marvel at them.


Other molecular examinations have revealed the ways octopuses are the same as us. Benny Hochner, a neurobiologist at The Hebrew University of Jerusalem, has studied the octopus memory. The octopus, like humans, seems to have both long and short-term memory separated into different parts of the brain. In an area of the brain that seems important for memory, he discovered long-term synaptic potentiation (LTP), a process that increases the strength of synapses between nerve cells. It’s thought to be a mechanism to explain long-term memory formation, and in humans, happens in our memory center, the hippocampus. When Hochner blocked LTP in octopus brains, he found that they couldn’t remember tasks as well as they did before.

Jean Boal, a professor of animal behavior and marine biology at Millersville University in Pennsylvania, and her collaborators have been studying what appears to be REM sleep in cephalopods. The underlying concept here is the same. If octopuses have it, that means they evolved it independently. “That would mean that it has a really fundamental important function that is needed,” she says. “It might help us try to narrow down what is going on in sleep that's so essential.

Not all octopus research has been as provocative. In his article, Engber noted that Hochner’s lab also found octopuses were slow learners in one experiment, and that with all their degrees of freedom, the way they walk is underwhelmingly simplistic and automated. He cites another paper that says that octopuses might not have very strong personalities at all, meaning all the anecdotal references from researchers about playful and gregarious octopuses could be only part truth, part anthropomorphizing.


But why hold octopuses to such high standards? Do we need them to be amazing learners and have distinct personalities to have them be an interesting candidate for comparative biology? Perhaps we’ve gone a bit over board in delighting in their antics, but it doesn’t make them unremarkable at all.

“If every animal is special, and each one has its own, unique intelligence, then why should we be any more enamored of the octopus than, say, the clownfish or the clam?” Engber writes.

Perhaps we shouldn’t. But the octopus still holds some bragging rights within the invertebrate kingdom, as its genome shows us. When it comes to "intelligence," Ragsdale says many in the field are wary of the word because of how it’s been misused. But he thinks it’s mostly the media that has been swept up by the “genius” octopus; I couldn’t find a researcher who was willing to anthropomorphize their intelligence. “We would tend to prefer phrases like: excellent problem solvers, very resourceful in their environment,” he says.

Plus, Grasso says comparative biology and psychology isn’t about directly applying our intelligence to octopuses, or vice versa. It’s just seeing how evolution solves problems differently, or more intriguingly, in the same ways. Our intelligence is not in competition with theirs; so we shouldn’t be judgmental if their behaviors don’t line up with ours, nor should we outright compare them when they do seem similar.

"The main message is that they have a very different organization to their brain, which is different from ours in just about every aspect except the fact that it has neurons and is bilateral," he says. "And yet all of these parts work together to produce a coherent, well-tuned organism that can handle its world. It’s the very best octopus that it can be in the world today, just like the human is the very best human in the world today."

Before I leave the octopuses at Brooklyn College, Grasso’s student drops a crab into the water. The octopus hasn’t eaten, and should be hungry, so we’re hoping he will come out from his corner. One arm unfurls halfway, but then rolls back.

I accept that I won't be having the encounter Montgomery had, when she met her first octopus: “Twisting, gelatinous, her arms boil up from the water, reaching for mine. Instantly both my hands and forearms are engulfed with dozens of soft, questing suckers.”

I don't take it personally. I hear that a few days later, the octopuses have adjusted to their new homes. They are now active, and ready to start learning. They have names too: Quasimodo and Queen (each new pair of octopuses gets named with the same letter).

Now Grasso will begin testing Quasimodo and Queen, not to see if they’re conscious, or rascals, or mischievous—but if they can learn new tasks and what they’re able to remember. It’s important for us to not project human qualities onto them, he says, but studying octopuses also reminds us that humans are not the only version of "smart" that exists out there.

“That gets at that basic definition of what intelligence is, and that’s why comparative psychology asks those really basic questions,” he says. “What intelligence is, what it isn’t, how far it can go. I’m enchanted to be able to understand what intelligence is by looking at many different examples, rather than in an arrogant way, saying: I know what intelligence is, it’s what humans do.”

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