In a tiled, windowless room at the University of Kentucky, Meagan Stetler and Toma Matott are playing with six beagles. The dogs trot around the room, wag their tails and poke Matott with wet noses as they look for the can of Cheese Whiz she holds. They look like pets, but they are laboratory animals, bred for research.
In this case, it’s an Alzheimer’s study sponsored by a pharmaceutical company, and UK officials say they can’t divulge any details about what’s happening to the dogs. When it’s over, the dogs will be euthanized, or sent to another lab for more testing.
It’s not easy to take care of lab animals, says Stetler, a lab animal technical supervisor, as she cuddles with one of the older beagles.
“It’s very hard, but that’s the whole reason to do it,” she said. “They give us their whole selves for the improvement of health for all of us, and they deserve to be loved.”
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Somewhere in the same lab are 45 monkeys, crab-eating macaques, that are being used for research on the hardening of arteries. UK wouldn’t allow Herald-Leader journalists to see them, saying that humans could pose a danger to the macaques’ health.
UK also conducts experiments on rabbits, guinea pigs, pigeons, zebrafish and axolotls (Mexican salamanders), although the vast majority of UK’s research animals — more than 26,000 — are mice. Thanks to breakthroughs in transgenic science, in which scientists can transplant genes, the role of mice has expanded, said Harold Stills, a microbiology professor and veterinarian who oversees the care of research animals on campus.
“Transgenic technology has made mice a very versatile tool,” Stills said. “They’ve replaced a lot of animals over time.”
The numbers and types of research animals at UK vary constantly, depending on the research projects. Sometimes, medical researchers work on wound care with pigs, Still said, or there will be sheep on the premises.
As with every other big research school, UK must meet stringent federal standards for animal research. They include minimizing pain and suffering, and proving that alternative research, including computer simulations, can’t be used instead.
“But the reality is that to get at questions that are really important for you and me, before a drug could come into human studies, we have to do some studies that require animals,” said Lisa Cassis, vice president of research at UK.
Most lab animals are bred for research purposes, Cassis said, and federal standards require getting the most information from each experiment so the number of animals needed can be reduced.
Still, the animals rights movement, bolstered by a growing number of studies about animals’ ability to sense pain and hunger, keeps pushing to greatly curtail or end most animal research.
UK and People for the Ethical Treatment of Animals recently butted heads in court over UK’s refusal to release protocols on how animals are used in classroom instruction. UK lost in Fayette Circuit Court, and officials haven’t yet decided whether they will appeal.
PETA’s request under the Kentucky Open Records Act was routine, said Kathy Guillermo, a senior vice president at PETA who oversees laboratory investigations. The information it seeks would allow PETA to work with UK on alternative teaching methods, Guillermo said. For example, PETA helped the University of California at Irvine develop a computer simulation instead of having students drill into the heads of live rats.
PETA, though, is opposed to all animal research.
“They will tell you how regulated they are and how the public should be confident all is well,” Guillermo said. “I just want to say that’s nonsense. There is a fair amount of paperwork, but there is no experiment that is illegal. Most of the federal oversight has only to do with housekeeping.”
PETA’s work coincides with controversy over experiment replication. Last year, the journal Nature found that in a poll of 1,500 scientists, 70 percent failed to reproduce another scientist’s experiments, with the highest rates in chemistry and biology. This problem is particularly acute with animal experiments, Guillermo said, and that is why researchers should work harder to find alternatives.
“I can say that in the beginning, our entire argument was ethical,” Guillermo said. “It is now largely scientific: There is so much science on our side about the failure of the animal model. Scientists are being unscientific by suggesting there’s only one way to do this.”
In the lab and on the farm
In a warren of UK labs, thousands of mice live in colonies of plastic cages, where their food, water and air intake is monitored every day. Some mice even live in “smart cages” that can monitor every time they eat, drink or move. The cages are lined with sawdust; the mice build nests of cotton and paper strips. Some have litters of babies huddled inside.
In a hallway, two posters show a series of pictures of mice and rats that display the mouse and rat “grimace scale,” so researchers can understand when they are in pain. Some receive painkillers and anesthesia as well.
“We do not treat mice any differently than dogs,” Stills said.
UK scientists also do a great deal of research to solve the diseases of agricultural animals that form so much of Kentucky’s economy. At Coldstream Dairy Research Farm, which adjoins the Coldstream Resarch Park off Georgetown Road, for example, scientists work with dairy cattle, experimenting with open barns and various kinds of bedding to increase their comfort, and presumably their milking productivity.
Coldstream also hosts a research study of poultry nutrition, a joint project between UK and Alltech, a global animal nutrition company based in Nicholasville.
“Most of our work is noninvasive,” said Nancy Cox, dean of the College of Agriculture.
Across Interstate 64/75, more than 200 horses roam on North Farm, a complex made up of Spindletop Farm, Maine Chance Farm and part of the original Coldstream. In the 1970s, UK established two research herds that exist to this day, expanded with the help of stallions including Zippy, a 20-year-old quarter horse.
Those herds are routinely used by UK researchers for work on infectious diseases and reproductive problems, including mare reproductive loss syndrome, a caterpillar-induced syndrome that causes mares to abort and that devastated the Thoroughbred industry in 2001. Six of 10 vaccines currently used to protect horses against infectious diseases were developed by UK faculty.
The herd mares are bred in the field and through artificial insemination, and they will start giving birth in the next few weeks.
“When the foals are born, we go out to the fields just to get them used to us,” said Martin Neilsen, an associate professor of equine parasitology. “It makes our work easier and safer.”
Neilsen specializes in parasites, particularly the numerous worms that plague horses of every breed. Right now, he’s working with UK’s herd of miniature horses to study the efficacy of combinations of de-wormers. It’s noninvasive research that mostly involves testing fecal matter. Some studies require blood tests from the horses.
An old carriage barn now is a laboratory, with a breeding shed on one side. Scientists can test sperm collected there.
“We stepped up our efforts out here about five years ago,” Cox said. “We do research we can stand behind.”
A lingering debate
UK biology department chairman Vincent Cassone works with mice, zebra finches and sparrows, mostly on how circadian rhythms affect overall health. He said UK’s veterinarians closely monitor the health of all research animals.
“They are constantly on us to make sure the animals are as comfortable as possible,” he said.
Cassone works with mice to study the intersection of sleep rhythms and gastrointestinal health. People who work night shifts have higher rates of colon cancer and bowel problems.
He and his colleagues have discovered that one of the bacteria in the gut has its own clock and synchronizes to human sleep clocks. That discovery could have huge implications for intestinal diseases. He also works with birds, because the genes that control the development of birdsong are similar to those that control human language acquisition.
“Basic research on animals can bring new knowledge which you cannot do with a computer model,” he said.
Other colleagues work with axolotls, Mexican salamanders that can regenerate lost limbs. Humans have nothing in common with salamanders, Cassone acknowledged, but understanding their regenerative abilities could teach humans how to restore movement to paralysis victims.
However, Cassone said, public support for animal research coincides with how closely people identify with certain animals, including monkeys or dogs. (A 2014 video posted by the Beagle Freedom Project of lab beagles touching grass for the first time has been viewed 4.3 million times.)
In 2011, the National Institutes of Health ended any research on chimpanzees in the face of intense public pressure after PETA and other groups publicized inhumane practices at a few research labs.
UK researchers worked with chimpanzees as early as 1959, when UK was awarded a contract to train chimpanzees for the Mercury space flight program in the old Wenner-Gren Laboratory.
John Gluck, the author of “Voracious Science and Vulnerable Animals: A Primate Scientist’s Ethical Journey,” began his academic career at the Wisconsin Primate Laboratory in the 1960s, working on a project that separated infant rhesus monkeys from their mothers and raised them in isolation. Over time, he wrote, he came to realize that scientists had an ethical responsibility toward the animals in their care.
Today, like Guillermo, he questions not just the ethical issues of primate research but its efficacy.
“I think what we’ve seen over the last 10 to 15 years is the accruing evidence of the ability to harm an animal,” said Gluck, an emeritus professor at the University of New Mexico and a faculty affiliate at the Kennedy Institute of Ethics. “If you look in the latter part of the 19th century, lab studies were done on fully conscious animals. There was so little belief that the animals really could suffer to the extent we now recognize they can. That’s a crucial piece: What does pain and distress accomplish in terms of interfering with the study?”
“What you’re seeing now is (that) the use of animals as a public health problem is starting to make itself known,” Gluck said. “The ability to translate research findings to the human clinical situation, we’ve been pretty glib about that, about how well those preclinical studies actually do translate to developing effective disease interventions to humans.”
Gluck and Guillermo would like to see a new national commission on animal research that re-examines rules, regulations and the ethics of animal research.
“Animals have been used in research for so long historically that a lot of uses are traditionalized, and you’re not even sure they’re necessary,” Gluck said. “It’s one of the problems with science in general is that it requires great creativity, but we get stuck in methodical ways of doing things. The research on animal alternatives is really pathetic.”
Nonetheless, a lot of breakthroughs in diagnosis and treatment start with animals, said UK’s Lisa Cassis.
“I don’t want them to test a drug on my child,” she said.
As of March 15, the University of Kentucky says, these animals were being used in 515 experiments, known as Institutional Animal Care and Use Committee protocols:
Division of Laboratory animal research
Mice: 26,350 (in approximately 9,413 cages)
Guinea pigs: 4
Non-human primates (Cynomolgus monkeys, or crab-eating macaques): 45
Animal and food sciences
Beef cattle: 654
Dairy cattle: 264
Spiny mice: 235
Zebra finches: 28