Squirrel monkey chirps filled a small ranch-style building in north Gainesville, Florida -- a chorus that made Kari Bagnall's smile swell even wider.
She covered her grin with a medical mask, calmly walked to the middle of a climate-controlled room and greeted each of the 26 monkeys. There were about three to each large cage.
Poppit and Pixel jumped over each other when Kari passed by. Gizmo looked up with wide eyes. Pip let out a tiny chirp.
Then there was Oak. Despite pain from rheumatoid arthritis, his energy was about as high as the others'.
Bagnall stopped interacting with the other monkeys to look directly at him. She squinted, homed in on his hands and then shifted her shoulders back with satisfaction.
"He looks good," she said.
Oak and the other monkeys arrived in mid-November at Jungle Friends, this primate sanctuary in Gainesville where Bagnall serves as founder and director.
The monkeys were once involved in a US Food and Drug Administration study intended to investigate the role of various levels of nicotine in the onset of addiction in teens and young adults.
In January, after the deaths of four monkeys involved in the research drew criticism from some animal rights activists, the agency ended the study. The 26 remaining monkeys were retired to Jungle Friends, and the FDA quickly established an Animal Welfare Council to oversee all animal research under the agency's purview.
The squirrel monkeys are the latest arrivals.
The common squirrel monkey, or Saimiri sciureus, typically can be found in the tropical forests of Central and South America, roaming from Costa Rica through central Brazil and Bolivia. These monkeys typically have a life span of about 20 years. The males weigh between 1.22 and 2.53 pounds on average, and the females average between 1.43 and 2.76 pounds.
When the monkeys arrived, Bagnall said, they all looked "gorgeous" and healthy, needing no serious medical care -- except for Oak, who the FDA had told the sanctuary had a diagnosis of rheumatoid arthritis and was receiving treatment.
Bagnall thanked the FDA for releasing the monkeys to her sanctuary's care.
"The most special thing about these particular monkeys is that they came out of the FDA, which has not released monkeys out of research in the past -- and we are so happy that now the FDA is opting to retire monkeys after the research has ended. They didn't have to do this," Bagnall said.
"All of these monkeys were born inside," she said. "They've never been outside. So they've never felt the sun on their face or the grass under their feet or rain or wind. It's all going to be such a new experience for them, and they're all just so different and individual. They'll all react differently."
For now, the monkeys are being kept indoors until spring, when they will be introduced to their new outdoor environment.
A 'scientific, ethical and economic' debate
The monkeys used in the nicotine addiction study are just a sliver of a larger debate around medical research on animals.
In the United States, 75,825 non-human primates were used in experiments at animal research facilities last year; an additional 34,369 were held in facilities but not used for study, according to the US Department of Agriculture.
As for the FDA's latest decision, animal rights activists celebrated the monkeys' arrival at their new retirement home in Florida.
Some scientists questioned what the move could mean for the future of medical research.
Matthew Bailey, president of the Foundation for Biomedical Research, said in January that "undoubtedly, some will argue that this recent action by the FDA is a reason to end research with animal models. But given the inextricable role humane and responsible animal research plays in the health of the overall population, and the health of the animals about which we care so deeply, that is a very dangerous proposition.
"Animals played a role in the development of each of the top 25 most prescribed drugs in America," he said, adding that pets, farm animals and wildlife benefit from medical treatments developed in part from animal research.
"Farm animals and wildlife are routinely vaccinated against any number of diseases, but those vaccines wouldn't be available without animal research," he said. "If you love animals, you really should support animal research."
While visiting Jungle Friends last week, Justin Goodman, vice president of advocacy and public policy for the taxpayer watchdog group White Coat Waste Project, said that technologies, including computer models, could replace animal models in research.
"The truth is that, for scientific, ethical and economic reasons, animal experimentation is incredibly wasteful and needs to go the way of the dinosaur," he said. "Technologies that replace the use of animals are more effective."
Adjusting to the outside world
When lab animals retire at sanctuaries, most people assume that they are immediately released outdoors to run free.
That's not often the case, Bagnall said, adding that a gradual introduction to the outdoors seems to benefit the animals more.
"You would think 'Oh, we're going to give them all this space and be outside,' but sometimes they're a little nervous about that, and they've never been outside," Bagnall said.
For the 26 squirrel monkeys, including Oak, Bagnall and her team are introducing them to the outdoors gradually by putting elements they will encounter -- such as banana leaves, bamboo, or pine straw -- in the monkeys' cages.
"So they get used to what things feel like and look like and smell like first," Bagnall said.
"It's a gradual process, and it will probably take four to five months," she said. "Then they're going to be released into their outdoor habitats."
Another reason the monkeys are not being released immediately to the outdoors is because of the cold winter weather, she added, and in the spring, they can adjust to the new climate.
Meanwhile, all of the monkeys undergo routine medical evaluations, with Oak requiring more specialized care.
Oak, who is 5 years old, has puzzled the Jungle Friends care team with his rheumatoid arthritis diagnosis, said Dr. Bobby Collins, a retired veterinarian who once oversaw the welfare of research animals in academic settings and now volunteers at Jungle Friends.
"This is unusual," said Collins, who has been treating Oak. "Because you just don't see squirrel monkeys or non-human primates having rheumatoid arthritis. It's not diagnosed very frequently, and this is a young animal. Most of the time, if you're going to see it in animals, it's older animals, where they've got chronic inflammation."
Oak has been treated with immunosuppressive drugs, and his care team plans to discuss his health with experts at the University of Florida to better understand his medical problem and needs.
"The kind of disease that this guy has, it flares up, and he obviously has discomfort and some pain associated with it. It alters how we house the animal and let him interact with the other animals," Collins said.
"That social interaction for non-human primates is so important. You can see these guys get depressed when they're deprived of contact with other animals their own species," he said. "So we want to try to remove those flareups or minimize them so he can, again, interact with monkeys and be a monkey."
On Wednesday afternoon, the monkeys had a "music hour" and listened to the soundtrack of "Forrest Gump" while playing in their cages.
Oak sipped from an in-cage water bottle before nestling into a corner with his tail curled over his shoulder. "Joy to the World" by Three Dog Night sang out across the room: "Joy to the fishes in the deep blue sea, joy to you and me."
In that moment, Oak appeared relaxed.
The road to retirement
The saga of Oak and the other squirrel monkeys began in 2014.
That year, the FDA's National Center for Toxicological Research conducted a study to examine the behavioral and biological effects of nicotine in squirrel monkeys. The research was an effort to better understand how reducing nicotine levels would impact them, and ultimately to better understand how it affects humans.
After learning about the study, White Coat Waste Project, an advocacy group working to stop taxpayer-funded animal research, filed a Freedom of Information Act request for materials related to that research. The group claimed that the response it received didn't comply with its request, and in August 2017, it sued the FDA.
About a month later, world-renowned primatologist Jane Goodall penned a letter to FDA Commissioner Dr. Scott Gottlieb noting that she was "disturbed" and shocked" to learn that the agency was still performing nicotine addiction experiments on monkeys.
Soon after, Gottlieb responded directly to Goodall, writing, "After learning of concerns related to the study you referenced, I directed the agency to place a hold on the research study earlier this month. Accordingly, at this time, all experimentation involving the monkeys in the study you referenced has been halted."
Because the study was terminated prior to completion, behavioral data from the research is incomplete, FDA spokeswoman Tara Rabin wrote in an email Monday.
If the study had been completed, the FDA still would have considered moving the monkeys to a sanctuary, she wrote. "In light of the decision to halt the study, the FDA currently has no plans to conduct additional squirrel monkey research."
According to the FDA's website, animals are sometimes used in the testing of drugs, vaccines and other biologics, and medical devices, mainly to determine the safety of these medical products.
When animal testing is done, manufacturers or sponsors are required to follow the FDA's regulation Good Laboratory Practice for Nonclinical Laboratory Studies. The agency also supports the use of Institutional Animal Care and Use Committees, federally mandated under the Animal Welfare Act, and the Health Research Extension Act to provide oversight for most institutions using animals in research.
In January, Rabin wrote in a separate email that individual animal care committees are tasked with study-specific oversight, but "the newly established Animal Welfare Council will track all studies across the FDA and provide centralized oversight and coordination of all animal research activities and facilities under the agency's purview. This Council will advise on the agency's approach to animal welfare issues and ensure alignment of animal studies with the agency's mission."
Additionally, in November, the FDA proposed a study aimed at finding ways in which drug developers could conduct certain types of research without dogs, in an effort to eliminate the use of dogs in certain trials.
"This is another example of our efforts to reduce animal research," FDA spokeswoman Nina Devlin wrote in an email Saturday.
The FDA has also taken steps to develop and use other research models that don't involve animals, Rabin said Monday, including forming a working group to accelerate adopting modeling and simulation tools.
"These are just some of the many FDA initiatives underway to reduce reliance on animal-based studies, while still helping to ensure that Americans have access to safe, reliable and effective medical products and safe food," she wrote.
Some politicians applauded the FDA's decision to terminate its nicotine study and establish a council to review future animal research.
"I'm proud that a Florida sanctuary stepped up to give these monkeys a home," Florida Rep. Matt Gaetz said in a statement Friday.
"There's still much more work to be done to stop the government's monkey business in labs at the FDA and other agencies."
As music hour at Jungle Friends wound down on Wednesday, The Youngbloods crooned, "Come on people now, smile on your brother."
Poppit and Pixel hopped over each other from one end of their cage to the other. Gizmo swung from a red barrel. Oak curled up calmly.
"Everybody get together, try to love one another, right now."
For now, the squirrel monkeys will continue to chirp and play in that small ranch-style building in Gainesville until it's finally time to go outside.