Humans are more closely related to dinosaurs than they are to octopuses. Our lineage split from that of cephalopods—the spineless class that includes octopuses, squids and cuttlefish—half a billion years ago. Octopus brains lack any of the major anatomical features of vertebrate brains, and most of the animals' neurons are distributed across their arms rather than in their head.
Yet octopuses are extremely intelligent, with a larger brain for their body size than all animals except birds and mammals. They are capable of high-order cognitive behaviors, including tool use and problem-solving, even figuring out how to unscrew jar lids to access food. Increasingly, some researchers are suggesting octopuses' combination of smarts and sheer difference from humans could make them an ideal model for inferring common rules governing complex brain function, in addition to revealing novel neurological workarounds cephalopods have evolved.
Scientists have often turned to animals, among them Drosophila fruit flies, zebra fish and Caenorhabditis elegans nematodes, to gain biological insight and understanding. But of all the widely studied “model species” that are easy to raise in the laboratory, rodents such as mice have been most instrumental in understanding how the brain works.
“The advantage of the mouse is that its brain is remarkably similar to the human brain, whereas the advantage of the octopus is that it's remarkably dissimilar,” says Gül Dölen, a neuroscientist at Johns Hopkins University. Comparing and contrasting these systems with our own, she says, “gives you that logical power of reduction.” Nematodes and fruit flies are also very dissimilar to humans, she notes, but octopuses eclipse these fellow invertebrates in terms of complexity. Recognizing the unique opportunity cephalopods provide as vastly different yet highly sophisticated creatures, Dölen and other neuroscientists are rooting for them to become the field's newest model organism.
Using octopuses to gain insight into our own species was originally proposed in the 1960s by neurophysiologist J. Z. Young. The idea moved within reach in 2015, when scientists sequenced the first octopus genome, for the California two-spot octopus. “A whole genome opens up huge levels of information you didn't have before,” says Clifton Ragsdale, a neurobiologist at the University of Chicago, who co-authored the octopus genome study in Nature.
As was the case with other model species, publishing the octopus genome paved the way for critical modes of investigation, the researchers say. These include using genetic engineering to probe how the brain works, zooming in on where specific genes are expressed, and exploring evolution by calculating differences between octopus genes and those of other species.
“We're at a really exciting moment for working with these remarkable animals,” says Caroline Albertin, an evolutionary developmental biologist at the Marine Biological Laboratory in Woods Hole, Mass., and lead author of the genome study. “There's just a vast ocean of research and questions that we need to explore.”
Toward that end, researchers have begun developing cephalopod versions of the same molecular tools that those working with mice or flies take for granted. Last summer in Current Biology, Albertin and her colleagues described the first cephalopod gene knockout (inactivating a gene to study what it does). Now the same team is working on gene knock-ins that will, for example, let scientists insert activity indicators into octopus cells. This process will let them study the animals' neural activity in real time, says Marine Biological Laboratory researcher Joshua Rosenthal, who co-authored the knockout study. “Once we get that next step,” he says, “I think the community is just going to start exploding.”
Research is already accelerating. In 2018 Dölen and co-author Eric Edsinger dosed octopuses with MDMA and found that although they are typically antisocial, they respond to a drug-induced flood of the neurotransmitter serotonin the same way humans do: they relax and become more sociable. Through genome analysis, the scientists also confirmed that octopuses possess the same serotonin transporters that MDMA binds to in vertebrates. As reported in Current Biology, this finding suggests that sociality could involve a molecular mechanism rather than being rooted in specific vertebrate brain regions.
Other labs are investigating how octopus arms sense and interact with their environment with minimal input from the brain. Last fall researchers reported in Cell that specialized receptors in octopus suckers detect chemicals on surfaces they contact, enabling them to taste by touching. “This is an example of how we need to consider studying life in all shapes and sizes to really understand how molecular and cellular adaptations give rise to unique organismal features and functions,” says Nicholas Bellono, a molecular and cellular biologist at Harvard University and senior author of the Cell study.
Scientists will soon have even more resources to draw on. In 2016 the Marine Biological Laboratory launched a cephalopod breeding program to culture research animals. Albertin and program manager Bret Grasse are now working with Dölen and other colleagues to sequence the genome of Octopus chierchiae—a golf ball–to tangerine-sized Central American species that is the leading candidate for an octopus model organism. O. chierchiae's small size would make it ideal for raising in a lab, and unlike a number of other octopus species, scientists have figured out how to breed it.
Cephalopods will no doubt bring more insights into fundamental biology. Technological breakthroughs could follow, too. Materials researchers are interested in the animals' skin for its incredible camouflage ability, for example, and computer scientists may someday draw on octopuses' separate learning and memory systems—one for vision and one for tactile senses—for new approaches to machine learning.
Octopuses could also inspire biomedical engineering advances. Rosenthal is studying cephalopods' incredibly high rates of RNA editing, which could someday lead to new technologies to erase unwanted mutations encoded in human genomes. Ragsdale is investigating how octopuses quickly regenerate their arms, nerve cords and all; this might one day contribute to therapies for humans who lose limbs or have brain or spinal cord damage. “Biology has pretty much figured out a solution to almost everything,” Rosenthal says. “We just have to find it.”