Using animals for science is more involved than it used to be.
June 2010-A decade ago, Johns Hopkins investigators who wanted to take care of their own laboratory mice might keep them in cages on a lab bench or tucked in a corner.
Today, things are different. Most mice are housed in a central facility on campus, and investigators who want to keep mice in their own facilities need to meet strict standards for satellite housing. To ensure pathogen-free colonies, a visitor entering these areas first must don a paper gown and shoe covers, step on a sticky floor mat and pass through a sealed door. Inside, the air is filtered. Other animal welfare rules dictate that the temperature and humidity in the satellite housing area be within set limits and recorded daily. The mice themselves must be checked every day.
Johns Hopkins earned the highest
possible commendation from AAALAC,
the organization that accredits
institutions using animals for science.
Photograph by Rama
“You can’t just leave a large amount of food and water for the mouse to last over the weekend, or even from Christmas Eve to December 26,” says Nancy Ator, the chair of the university’s Animal Care and Use Committee.
More rigorous attention to satellite housing is one of many changes that the university has instituted in its lab animal program in recent years—changes that reflect its efforts to meet high standards for the care and use of these animals.
This past year, those efforts led the university to earn the highest possible commendation from AAALAC International, the private organization that accredits universities and other institutions using animals for science. Following its triennial site visit in June 2009, AAALAC—the Association for Assessment and Accreditation of Laboratory Animal Care International—awarded the university full continued accreditation and concluded that Hopkins had no issues requiring corrections.
Accreditation is no small feat. Hopkins houses almost 150,000 laboratory animals across its campuses, 97 percent of which are mice and rats. In its site visits, AAALAC examines everything from the size and cleanliness of animal cages to the expiration dates on bottles of drugs. A few expired bottles of a sedative or analgesic designated for animal use could jeopardize accreditation, Ator says.
"Regulations are kept to the word," says Chris Zink, director of the Department of Molecular and Comparative Pathobiology, which includes veterinarians responsible for the care and welfare of Hopkins' research animals.
The university is also subject to at least annual unannounced inspections by the Animal and Plant Health Inspection Service of the U.S. Department of Agriculture (USDA), the agency that enforces Animal Welfare Act regulations. These rules, which must be strictly followed, cover most warm-blooded species but exclude rats and mice that have been bred for research.
For many at Hopkins, it may seem as though the bar has been rising steadily. But is that the case?
Yes and no, explains Ator.
She says regulations themselves have not changed significantly in the past decade. However, external inspectors frequently shift their emphasis or change internal rules to influence what is required.
For example, while USDA regulations mandate "good veterinary practice," what that constitutes isn't spelled out. So the agency issues interpretative rules—for instance, forbidding analgesics to be administered after the expiration date.
"AAALAC and USDA both are continually tweaking their expectations in response to new information about what animals need," Zink says.
Other external factors include pressure from animal rights groups, which have influenced regulatory bodies to enforce animal research laws more vigilantly.
Hopkins' own efforts over the last decade to enforce federal requirements internally have also added to the sense of rising expectations.
As the result of a 2000 site visit, AAALAC placed the university on probation, citing a lengthy list of problems related to the structure and oversight of Hopkins' animal program. The next year, Hopkins overhauled its program.
It consolidated three animal care and use committees—from Medicine, Public Health and Homewood—into one university-wide body, a merger that eliminated inconsistent standards in the groups responsible for overseeing animal research protocols. Hopkins also separated the leadership of the Animal Care and Use Committee from the leadership of the animal services program.
Previously the same people were running both groups, says Ator, “so inspection by the committee was like being called on to check your own house.”
Among other changes, the administration also increased the number of full-time positions for animal care workers and supervisors and boosted the salaries for those positions to try to reduce what had been a high turnover rate. And it introduced mandatory training classes and examinations for animal caretakers.
Overall, many who use animals for research or oversee their care say the higher expectations brought about by such changes are a good thing, both for animals' well-being and for science.
“Overwhelmingly, things have improved,” says Professor of Physiology Roger Reeves. “Animals now are better cared for. And science is done better when animals are cared for better.”
Rodents used as sentinels, for example, are tested for a broad array of pathogens, including some organisms that don't pose a threat to animal health but could compromise scientific results.
In addition, says veterinarian Robert Adams, director of laboratory animal medicine for Research Animal Resources, “all our mice are kept in sterile cages. That’s not mandated by law; it’s mandated by us because disease can derail your research.”
But many who use lab animals or oversee lab animal programs also say certain policies and expectations are unnecessary or even contrary to the mission of the humane use of research animals.
Scientists such as Reeves, for example, question the merits of a policy on the method for sacrificing mice. According to NIH requirements, scientists usually must first anesthetize a mouse before sacrificing it through cervical dislocation. But anesthesia itself distresses the mouse, says Reeves. Cervical dislocation alone “takes less than one second,” he says, and is a practice that many scientists consider the most humane way to sacrifice a mouse.
Another issue involves the use of environmental enrichment required by the Animal Welfare Act. Research facilities must provide enrichment (such as toys and social housing) for nonhuman primates and exercise opportunities for dogs. At Hopkins, several other species routinely receive enrichment.
But AAALAC has ramped up those expectations and is scrutinizing enrichment for a longer list of animals, such as laboratory frogs.
Ator points out that the emphasis of AAALAC site visitors has shifted as various aspects of animal care—such as satellite housing—have improved. "It’s the perfectibility factor,” she says. “Like in a house, when the carpeting is replaced and looks good, then the curtains look terrible.”
Ator and others in the field expect new issues to be addressed in an updated version of the "Guide for the Care and Use of Laboratory Animals." Published by the National Research Council, the guide is the gold standard for designing appropriate programs for animal research, and recipients of federal research funding must follow it. A National Academy of Sciences committee has spent the past two years on the update, which is intended to incorporate new scientific knowledge acquired since the last guide was issued, in 1996.
Many scientists in the field anticipate significant changes, such as an expanded section on enrichment and a longer list of species recommended to receive it. The updated guide is expected to be published sometime this year.
The Mouse Model: Less than Perfect, Still Invaluable