Broad regulations define bounds for animal researchers

Dan Haugen

Dressed head-to-toe in hospital scrubs, Dr. Richard Bianco and his assistants diligently snip and stitch away in the open chest cavity in front of them under a flood of light from overhead. When requested, others fetch tools from a table full of specialized clamps, tweezers and scissors at the foot of the operating table, and two more monitor vital signs, such as temperature and oxygen levels.

The team’s subject, completely covered in towels except for the half-foot square of exposed innards, is a four-month-old adolescent sheep.

Bianco and his team at the University’s Experimental Surgical Services have been hired by the makers of a new artificial heart valve to test out the device in an animal. Like virtually all medical developments in the developed world, the transplant must fare well in animal studies before the Food and Drug Administration will approve it for human trials.

“We do it the same way you would do it in humans,” Bianco said, “which is why we’re required to use larger animals, so it will fit. We mimic the clinical situation.”

If the artificial heart valve is successful in the sheep, the procedure moves one step closer to FDA approval. If it performs poorly, the company will head back to the drawing board. Either way, the University will have brought in approximately $8,000 and provided valuable operating room experience to Medical School students.

Many animal rights activists argue that University research such as this, using animal subjects, is unethical and unnecessary. But those doing the work insist that its benefits far outweigh the sacrifices. In fact, that is the case University researchers must make to regulators before they undertake any experiment involving animal subjects.

Research regulation

there was a time when conducting experiments on animals was as simple as stopping by the local pet store, picking up a batch of mice or rabbits and going ahead with the work.

That was also a time of horror stories for animal welfare advocates. Life magazine exposed one in 1966, with photographs of dogs enduring grossly cramped and unsanitary conditions. The wave of public outcry that followed culminated in passage of the Animal Welfare Act by Congress.

The University Board of Regents adopted its first animal care and usage policy in 1978. The four-page document is deceptively thin, and actually refers to hundreds of pages worth of federal policy such as the Animal Welfare Act.

From cage or holding-pen size to dietary and nutrition concerns, just about every aspect of animal use is regulated.

As the University’s Institutional Official for Animal Care and Usage, Bianco is charged with seeing that he and other researchers follow every rule. Bianco said one of the biggest misconceptions he hears from animal rights activists is that there are no rules.

Justifying use of subjects

all use of research subjects, animal or human, must be internally OK’d by the University’s Research Subjects Protection Programs.

Researchers requesting the use of human subjects must get approval from the Institutional Review Board and those wishing to use animals must be cleared by the Institutional Animal Care and Usage Committee.

“They are looking at the risks and benefits of the research,” Director Moira Keane said of the committees.

The process starts with paperwork. Investigators must complete a 30-page animal research form off the programs’ Web site.

The application asks for a detailed description of the research being conducted, including how it will advance scientific knowledge, how many and what type of animals will be used and what will be done to the animals. If the animals are expected to experience any pain or distress, applicants must explain what steps will be taken to alleviate it.

That information is then passed to members of the animal care and usage committee, which considers all of those questions when making decisions at their twice-monthly meetings.

“We look very carefully at whether or not animals will be suffering pain or distress,” Keane said. “I think that’s a misunderstood component. Researchers take every step possible to alleviate the pain or distress.”

Currently, there are 17 committee members, all appointed by the University’s institutional official for animal care and usage. Members of the Student Organization for Animal Rights have complained that the meetings take place behind closed doors, but Keane said they cannot be open to the public because of concern for intellectual property rights.

For each application, the committee discusses the merits and possible alternatives to animal use.

“One of the primary aspects of the animal review is whether or not the researcher has demonstrated an exploration of alternatives,” Keane said.

Before animal use is approved, researchers are expected to have exhausted other methods, like using tissue cultures or computer models.

If that has happened and the committee is also certain the experiments wouldn’t be needlessly reproducing work that has already been done, it generally approves the project, possibly with stipulations.

Most proposals reaching the committee are approvable, Keane said. Investigators know what is expected and typically have their proposals peer-reviewed before submitting them, she said.

Getting the animals

oInstead, they place an order with the University’s Research Animal Resources, the department responsible for purchasing and caring for all animals used in research projects.

“We don’t have any stock animals on hand waiting for assignments,” Director Cynthia Gillett said.

After the animal care and usage committee approves a project, Research Animal Resources coordinates with the committee and the researcher to facilitate the delivery.

The animals are bred for laboratory use by a handful of vendors certified by the Department of Agriculture from across the country. Gillett said laboratory mice sales in particular add up to big business.

The University used 113,000 mice during the 2000-01 fiscal year, the most recent year for which statistics are available. That year, the institution also used more than 200 nonhuman primates, 300 sheep, 600 dogs, 900 rabbits and 1,000 pigs. Those figures include animals used in research, teaching and other services at all University campuses.

Small animals like mice and rats make up the overwhelming majority of animals used in research. Cancer research has been largely dependent on the availability of laboratory mice.

Bigger animals are needed in some research. Sheep are commonly used in cardiovascular research like Bianco’s. Nonhuman primates are handy in behavioral studies.

Animals are housed all over campus – not for security reasons, but for the convenience of researchers, who are also spread out.

Regardless of location, each cage and holding pen gets a daily visit from one of Research Animal Resources’ 100-plus employees.

Gillett said the checks serve several purposes. As workers make sure the animals have sufficient food and water and also look for signs that the animals are being used according to protocol.

Each cage has an identification number, which is used to keep track of veterinary records.

Not emotionally sterile

you have to understand, the people who work with these animals – particularly primates – get enormously attached,” said Timothy Ebner, a professor of neuroscience who uses rats, mice and nonhuman primates in his own research.

“They interact with these animals much more than you ever would with your pet,” he said.

In his research, Ebner is trying to better understand how the brain processes motor functions.

Primates have a nervous system very similar to humans, Ebner said, but the advantage of using animals is that we can better observe what’s going on inside the brain using surgical methods that would be unacceptable on humans.

Ebner and his colleagues implant tiny electrodes in the primates’ brains so while they observe the animal’s behavior, they can simultaneously see what is going on inside single brain cells.

Ebner said he has put up with periodic harassment from animal rights activists for several years, but he still stands by his work.

“You may think it sounds pretty abstract and maybe just academic, but in fact it has led to at least completely new treatments for Parkinson’s disease,” Ebner said of research like his across the country.

Bianco echoed Ebner’s words.

“We don’t like to lose our animals. Ninety percent of our employees have their own pets. These are not animal haters; these are animal lovers,” he said.

“Cancer isn’t a death sentence anymore. That’s because of medical research using animals.”


Dan Haugen covers University research and welcomes comments at [email protected]