WOODS HOLE — Their donut-shaped brains are the largest of any invertebrate on the planet. Their eight highly flexible arms each have hundreds of suckers and millions of neurons that can sense their surroundings, as if they were a human nose, tongue, and fingers fused together.
Octopuses can use their unique physiology and sensory perception to camouflage themselves instantly, edit their genes, navigate tricky terrain, and engage in complex problem-solving.
Those uncommon abilities have led scientists at the Marine Biological Laboratory to conduct more research on octopuses and other cephalopods than anywhere else in the world. Their goals range from finding treatments for neurodegenerative diseases, such as Alzheimer’s, to developing robotic tools that can snake through tight spaces.
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“We don’t know whether our understanding of cephalopods will transform society, but we know they do a lot of unique things that could,” said Josh Rosenthal, a senior scientist at the laboratory, which is run by the University of Chicago. “They could be key to unlocking a whole new area of biology.”
But the qualities that make them such valuable research subjects have also made them increasingly controversial.
As more studies reveal the intelligence of cephalopods and explore their perceptions of pain, wildlife advocates have pressed regulators to do more to protect them and require that researchers abide by the same rules they must follow when experimenting on vertebrates.
In recent months, lawmakers have stepped up pressure on the National Institutes of Health, which pays for most biomedical research in the United States, to issue rules similar to those in Europe, Canada, and Australia that regulate how researchers treat the complex creatures.
In a letter this fall, Representative Seth Moulton, a Salem Democrat, and more than a dozen members of Congress urged top regulators to update federal rules on the humane care of laboratory animals to include cephalopods. They also called for new federal guidelines on how researchers handle them in labs.
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“These incredibly intelligent animals are being denied basic humane treatment with no avenue for accountability,” the lawmakers wrote, noting that an increasing amount of research is being done on cephalopods.
The existing federal rules require researchers who are experimenting on vertebrates, such as rats or mice, to provide appropriate housing, nutrition, and medical care, as well as to do their best to minimize the animals’ pain.
In a follow-up letter, Senator Cory Booker and three other senators added that “a wealth of evidence from recent research demonstrates that cephalopods stand out from other invertebrates, in terms of their intelligence and capacity for pain, two criteria historically used to justify humane treatment requirements in research.”
The letters follow a petition filed with the NIH two years ago by Harvard’s Animal Law & Policy Clinic and a coalition of advocacy groups, including the New England Anti-Vivisection Society. They raised concerns about a Marine Biological Laboratory program that involves breeding and selling cephalopods at all stages of their lives, with no requirements for how they’re treated.
It urged the NIH to regulate experiments that deprive them of food, shock them with electric prods, and use invasive procedures that could cause pain.
“United States animal welfare policy is falling behind and failing these precious animals,” said Catharine Krebs, a medical research specialist with the Physicians Committee for Responsible Medicine, one of the petitioners.
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More than two years since they filed the petition, federal regulators have taken no action to protect cephalopods.
In response to questions from the Globe, David Kosub, a senior advisor at the NIH, said the agency continues to study the issue and was “aware of the standards in other countries that include cephalopods in animal welfare oversight.”
“We are still reviewing options for providing guidance on humane care and use of invertebrates in NIH-funded research,” he said. “Throughout this process, we are committed to promoting the best possible care and use of the animals … while ensuring oversight of research with animals is based on scientific evidence focused on animal welfare.”
At the Marine Biological Laboratory, whose researchers won a Nobel Prize in 1963 as a result of squid experiments that documented the nervous system’s electrical activity, some scientists worry that changes in federal rules could hamper what they consider to be vital research.
Diana Kenney, a laboratory spokeswoman, said researchers at the facility comply with federal rules to protect vertebrates.
Kenney cited the laboratory’s “strict internal policies” for cephalopod research, which she said seek to “ensure their ethical and humane treatment.”
The policy, she added, requires all researchers at the laboratory to receive training for handling cephalopods, and that a special committee approve all such research. The laboratory is working “with the greater cephalopod research community to develop a framework for national policies, grounded in science, for the ethical treatment of cephalopods,” she said.
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Part of the challenge of achieving a consensus on what constitutes ethical treatment is the limited understanding of how cephalopods experience pain.
“It’s a loaded subject,” said Roger Hanlon, a senior scientist at the laboratory, who has a Navy grant to study octopuses’ arms, with the goal of helping engineers build more agile robots.
Pain has “an emotional component to it, and trying to understand emotion in animals is almost impossible,” he said.
Numerous studies have looked into whether cephalopods feel pain and have documented their avoidance behavior, such as trying to escape when anesthetized with certain chemicals and learning to avoid objects that produce electric shocks.
But Hanlon said there’s no way of knowing that their avoidance of “noxious stimuli” is equivalent to feeling pain.
Other scientists suggested that new rules could be superfluous.
“Everyone I know, including us, is adhering voluntarily to the same regulations,” said Rosenthal, who has spent years studying how cephalopods can edit their genes.
He worries about the details of any new rules. “The difficulty is knowing what the rules should be for organisms that are so different,” he said.
Other scientists who study cephalopods were less conflicted.
“I see strong evidence that cephalopods warrant protection,” said Robyn Crook, an associate professor of biology at San Francisco State University, who has spent nearly 20 years studying whether the animals perceive pain.
“There is a continuing lack of knowledge on best practices for managing pain and distress during invasive procedures, but this is something that could also be said about some vertebrate clades, such as fish and amphibians.”
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Dr. Steve Niemi, director of the Animal Science Center at Boston University, called the intent to protect cephalopods “commendable,” but he urged regulators not to act hastily.
“We still don’t have enough facts,” he said.
For example, it remains unclear how often cephalopods’ tanks should be cleaned, or what the optimal temperature of the water should be, or what’s the proper dose of an anesthetic, he said. Moreover, it’s unclear whether there should be separate rules for squid and cuttlefish.
“How we maintain these animals in a safe, healthy environment isn’t always clear,” he said. “We need to proceed carefully, and we need evidence-based criteria.”
In a humid room inside the Marine Biological Laboratory recently, a 15-month-old octopus known as Marco Polo was munching on a crab in a small tank covered by a lid, with three bricks holding it down. Octopuses, which can squeeze through holes the size of a dime, could easily escape their tanks without such measures.
The researchers there shared stories of being inked, sprayed with jets of water, and bitten.
In a larger room, beyond a jokey sign that warns those entering to “Beware of Octopus,” scores of tanks contained as many as 4,000 cephalopods, the vast majority of them hatchlings. Adults often have to be in their own tanks, as they can be cannibals.
Bret Grasse, who oversees the laboratory’s cephalopod operations, said he has “learned to speak cephalopod,” understanding when they need more food, space, or a tank mate. He judges their health by their appetite, movement, and respiration, among other things.
His staff pumps in large amounts of seawater, adjusts the lights in the room to account for day and night, and tries to make the cephalopods’ tanks simulate their natural habitats.
But many of the cephalopods there will be sold to other research centers and aquariums, with pygmy zebra octopuses earning the laboratory about $500 each and embryos going for as little as $10 apiece.
The laboratory requires buyers to sign an agreement promising to treat the cephalopods ethically, Grasse said, but they have no way of knowing what becomes of them after they leave.
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David Abel can be reached at david.abel@globe.com. Follow him on Twitter @davabel.