VALLEJO, Calif. — The adolescent patient turned sullen and withdrawn. He hadn’t eaten in 13 days. Treatment with steroids, phenobarbital, and Valium failed to curb the symptoms of his epilepsy. Then, on Sept. 18, he had a terrible seizure — violently jerking his flippers and turning unconscious in the water. Cronutt, a 7-year-old sea lion, had to be rescued so he didn’t drown. His veterinarian and the caretakers at Six Flags Discovery Kingdom began discussing whether it was time for palliative care.
“We’d tried everything,” said Dr. Claire Simeone, Cronutt’s longtime vet. “We needed more extreme measures.”
On Tuesday morning, Cronutt underwent groundbreaking brain surgery aimed at reversing epilepsy.
If successful, the treatment could save increasing numbers of sea lions and sea otters from succumbing to a new plague of epilepsy. The cause is climate change.
As oceans warm, algae blooms have become more widespread, creating toxins that get ingested by sardines and anchovies, which in turn get ingested by sea lions, causing damage to the brain that results in epilepsy. Sea otters also face risk when they consume toxin-laden shellfish.
The animals who get stranded on land have been given supportive care, but often die. Cronutt may change that.
“If this works, it’s going to be big,” said Mariana Casalia, a neuroscientist at the University of California, San Francisco, who helped pioneer the techniques that led to a procedure that took place at a vet surgery center in Redwood City, Ca.
That procedure was done by three neurosurgeons at U.C.S.F., who ordinarily operate on humans. During the operation, they bored a small hole in Cronutt’s skull, inserted an ultrathin needle into the hippocampus of the sea lion’s brain, then implanted embryonic brain cells extracted from a 35-day-old pig. These so-called “inhibitory cells” tamp down the electrical activity in the brain that leads to seizures, a process identified by Scott Baraban, a professor of neurosurgery who runs the lab where Dr. Casalia works. Over a decade, their technique has proved effective in curing epilepsy in mice.
Dr. Ryan Kochanski, left, Dr. Mariana Casalia and Dr. John Andrews perform the procedure on Cronutt. Dr. Casalia developed the cells and procedure used in the transplant. Credit…Claire Simeone
Cronutt, the first higher mammal to get the treatment, emerged from the surgery and anesthesia midday and was breathing on his own, the first step. Whether the surgery successfully reverses his condition won’t be known for several weeks.
Pig cells are important because they have properties of higher mammal species, including the sea mammals succumbing to epilepsy. And sea lions and sea otters are increasingly at risk for the disease.
The widely documented phenomenon, first discovered in 1998, led to a surge in beaching of sea lions in 2002, another in 2015, and annual summer beachings. By now, thousands of sea lions have been poisoned by the toxin, called domoic acid. It depletes inhibitory cells that ordinarily help offset excitatory cells in the brain’s electrical system. When those cells get out of balance, seizures result.
The same phenomenon has led to the closure of crab fisheries to prevent people from eating domoic acid-laden crabs and contracting a condition called amnesic shellfish poisoning.
In sea lions, scientists have used brain imaging to document how the toxins also lead to degradation to a part of the brain called the hippocampus that is involved in memory, navigation, and other functions. When sea lions show up on Pacific Coast beaches in the summer, some exhibiting seizures get rescued and are given supportive care, but they often die.
Researchers first discovered Cronutt after he ran aground in November 2017 in San Luis Obispo, Calif., and walked into a parking lot where he was deemed a “traffic hazard.” He didn’t seem sick. They tagged him for future reference and released him a few weeks later.
Shortly after, a bit further north in Marin County, he was identified on a beach where he walked up to several residences and climbed on porches and tables. This time, he took himself back out to the water, and then a week later was found on Ocean Beach in San Francisco, disoriented. “A member of the public reportedly tried to feed him a burrito,” according to a written chronology provided by Dianne Cameron, the director of animal care at Six Flags Discovery Kingdom
Ms. Cameron would ultimately become his caretaker after Cronutt — named for the pastry that is a combination of croissant and doughnut — showed up again on a beach in January 2018, this time in Sonoma County. He stood in front of a public beach bathroom, blocking access. Shortly after, at the Marine Mammal Center in Sausalito, Calif., he was deemed un-releasable because he wasn’t eating, and had shown up multiple times on land. Then he had a grand mals seizure.
The researchers couldn’t find a zoo home for the damaged animal. The National Marine Fisheries Service called Ms. Cameron at Six Flags and asked if she’d take him in because the park has facilities to care for rescues and history of adopting animals with medical issues. She didn’t hesitate.
“He’s such a sweet boy,” she said. At Six Flags, he didn’t perform as most of the other sea mammals there do, like Pirate, a harbor seal, or the 500-pound Wyland and Shark Bite, both sea lions. Cronutt kept having seizures and intensifying and more frequent cycles where he’d just stop eating for a while and grow particularly inattentive, behavior that the vets attributed to damage to his brain. His weight fell from a high of 255 to 175 pounds.
After his latest terrible bout, on Sept. 18, Ms. Cameron “went home and prayed that he’d make it through the night.”
In the ensuing days, she and Dr. Simeone began discussing whether it was time to euthanize Cronutt.
“Then my husband said: you’ve got to call Scott!” Dr. Simeone said.
Her husband, Dr. Shawn Johnson, also a vet, was referring to Dr. Baraban, the researcher at U.C.S.F. His lab had previously been in contact with the couple and the Marine Mammal Center because they knew about the problem in sea lions and felt they were ready to move up the food chain with their experiments.
Dr. Baraban said the surgery, even if successful, wouldn’t help people with epilepsy anytime soon because of the challenges of using pig cells in human brains as well as other factors.
“My immediate hope is to help the sea lions and sea otters,” he said.
On Monday, the day before the surgery, Cronutt appeared to be entering another difficult phase. His appetite had fallen sharply, despite energetically throwing his red ball, and splashing in the water.
Ms. Cameron occasionally approached him with a herring that had his anti-seizure medications stuffed inside its dead maw. “C’mon, Cronutt,” she implored. But the sea lion just took the fish into his mouth and spat it out again.
The damaged brain tissue appeared to be interfering with the signal telling him to eat. Ms. Cameron could see a dull tint to his dark-walnut eyes, not bloodshot and droopy as they sometimes get, but ominous.
She reflected on the upcoming surgery, the results of which won’t be known for 30 days when researchers see if his behavior bounces back as it has with mice and rats in prior work.
“Even if it doesn’t work, and there’s a chance it won’t work,” Ms. Cameron said, pausing and starting to cry before gathering herself, “maybe Cronutt’s purpose is to educate that there are toxins in our water and our ocean needs our attention.”
On Wednesday morning, the day after surgery, Cronutt still seemed to have no appetite at first. Then he started barking. Ms. Cameron approached with food, and Cronutt devoured two pounds of herring over the course of the morning.
“He ate, followed me all around, was super engaged, and really alert. I think he feels really good, considering he had a drill in his brain just yesterday,” Ms. Cameron said. “His eyes look beautiful.”