The cuttlefish was refusing to cooperate.
Close relatives of squids, cuttlefish are camouflage experts that can dramatically alter their skin textures and colors. Biologists at the Marine Biological Laboratory in Woods Hole, Mass., put cuttlefish into a tank filled with black and white pebbles. Most of the subjects hunker down, become black and white, and fade into the background.
Not this one. It swam laps, curled two arms upward, turning them cranberry-red, and squirted a plume of ink.
The researcher sighed. So went another afternoon at the laboratory, where scientists are raising thousands of octopuses, cuttlefish and their kin as part of an initiative to transform them into the next lab animals.
Cephalopods ooze scientific appeal: They have complex bodies, unusual genetics, impressive spatial skills and intelligent minds.
And they are one of the only animals known to so frequently subvert a basic process of molecular biology. As a rule, cells turn DNA sequences into RNA and transform this RNA into proteins. But cephalopods use enzymes to edit genetic information in RNA, usually to make new proteins in their neurons. Neurobiologist Joshua Rosenthal predicts RNA editing could be adapted for human therapeutic purposes, such as temporarily shutting off a cell’s ability to signal pain.
Yet the animals can be reluctant to breed, hard to raise and difficult to keep from escaping their tanks. Few laboratory protocols — and, in the U.S., no legal regulations — offer guidance.
Cephalopods “are considered the most alien form on the planet, the only invertebrate capable of higher-order cognitive tasks,” said Erica Vidal, a marine scientist at the Federal University of Parana in Brazil.
In January, the Marine Biological Laboratory announced that it was the first facility to raise multiple generations of pygmy zebra octopuses. “This is the first effort to go make a genetically tractable model,” meaning a species with cataloged and manipulable genes, said Rosenthal, who leads the lab’s cephalopod initiative.
Cephalopods are of Earth but apart from us. To find the last common ancestor of cephalopods and humans, we must travel back more than 800 million years. Some kind of tiny worm, probably, wriggles at the roots of this family tree. As the tree splits, fruit flies, leeches and squid arise on one side. On the other are mice, Tyrannosauruses and great apes.
Neuroscientists probe cephalopod brains to examine what arose on their side of this evolutionary chasm. Five hundred million neurons, about as many as in a rabbit, make up the nervous system in a common octopus. The majority are packed into the creature’s eight arms, not its brains, suggesting a decentralized intelligence in which arms are involved in making decisions.
“If we can make contact with cephalopods as sentient beings, it is not because of a shared history, not because of kinship, but because evolution built minds twice over,” wrote philosopher Peter Godfrey-Smith.
Cephalopods are “fantastically bizarre. They have these amazing behaviors,” said Caroline Albertin, a developmental biologist. “They’ve got these beautiful, weird body plans.” Three hearts, pumping bluish blood, beat within an octopus. A doughnut-shaped brain encircles its esophagus.
They are picky eaters and acutely sensitive to water conditions. They have thin skin — in some cases, a layer of skin a single-cell thick separates the animal’s internal body chemistry from its external environment.
And that characteristic is part of their appeal, such as when neuroscientist Gul Dolen and Eric Edsinger, a cephalopod scientist, in 2018 bathed five octopuses’ in liquid MDMA, or ecstasy. The animals, which typically avoid other octopuses, seemed to relax while drugged. This result, they concluded, suggests that octopuses have molecules in their brain cells similar to our serotonin receptors.
Less than an hour after the journal Current Biology published the study, People for the Ethical Treatment of Animals’ Julia Baines condemned the research as “indefensible, curiosity-driven nonsense.”
But biologists continue to expand their toolboxes. A handful of animals — small and quick to breed, such as mice or flies — dominated laboratory science for most of its existence, but that is changing. Scientists are raising frilled salamanders that don’t scar, lampreys that regenerate their spines and microscopic animals, called rotifers, that steal genes from plants. In 2018, researchers inserted the gene-editing system CRISPR into squid embryos.
Rosenthal imagines a scientist traveling, from the world over, to what he called a cephalopod “supercenter.” Then the researcher returns home with fresh data, made possible only by the most alien forms on Earth.