VETERINARY RESOURCES PROGRAM:
STEERING NIH'S ARK INTO NEW WATERS

by Rebecca Kolberg

There's no room for more animals. It costs too much. All it does is provide housing. Those are just a few of intramural scientists' perceptions - and misperceptions - about NIH's Veterinary Resources Program that the center is working hard to change.

C. Max Lang, who took the helm of the Veterinary Resources Program (VRP) last October, doesn't fault researchers for expecting VRP to do a better job than it has in the past. "Our primary goal should be to provide the most humane animal care and the highest quality service at the lowest possible price," he says.

Currently, VRP cares for about 75% of NIH's research animals - about 25,000 rodents, 500 rabbits, 400 pigs and ungulates, and 1,500 nonhuman primates - at 19 buildings in Bethesda and nearby Poolesville, Md. The remainder of the animals are cared for at institute, center, and division facilities or at contractors' facilities.

Upon arriving at NIH from Pennsylvania State University's Animal Resource Facility in Hershey, Lang found that his calculations supported intramural scientists' claims that VRP costs were steeper than at comparable biomedical research institutions. He also discovered that VRP had space-allocation policies that created a shortage of space for some species of animals, such as nonhuman primates, while they created an excess of space for others, such as rabbits. As part of an attempt to address both of those problems, Lang has redeployed staff and also changed VRP's practice of dedicating each building to a single species.

C. Max Lang

"We have room now. We want to get the word out to scientists that they can come back," says Lang, noting that many intramural researchers had turned to off-campus contractors for animal care when they ran into space problems at VRP.

In addition to more efficient use of space and staff, other cost-cutting measures implemented by Lang include coordinating the purchase of commonly used supplies. Previously, each VRP building ordered its own supplies. Lang is also taking a hard look at the environments in which the animals are kept to see whether some relatively expensive "containment" housing, which provides each animal cage with its own filtered air supply, can be replaced with less costly conventional housing that has a common air supply for a whole room of cages.

But housing is far from the only service that VRP can provide. VRP manages a repository of more than 350 strains of genetically defined rodents and rabbits for distribution to researchers and also assists intramural researchers in selecting appropriate models and in characterizing strains. It can also help researchers procure appropriate animal models from commercial breeders. In addition to monitoring animal colonies for infectious disease and pathogenic entities, VRP's veterinary staff can perform or assist NIH researchers with radiographic procedures and experimental surgery at the program's centralized facilities.

NHLBI's Daisy Lazarous, who, as part of Ellis Unger's team, has interacted with VRP on preclinical studies of angiogenesis for ischemic heart disease, says the VRP staff in general, and veterinarians John Bacher and Victoria Hampshire in particular, "have been extremely crucial in our ability to carry on our animal studies and collect meaningful data."

"There never has been a problem in scheduling surgery using Dr. Bacher's facilities - however intense the pace, in using radiology facilities, or in postoperative care by Dr. Hampshire's staff," says Lazarous, who, in contrast, has often encountered problems scheduling the use of radiology and surgery facilities through other animal services. Lazarous credits the free exchange of ideas for the good working relationship that her group has developed with VRP staff. "They give us adequate feedback regarding our protocols and problems and, in turn, are very amenable to suggestions from us. "

Still, as Lang notes, many intramural researchers remain unaware of the wide array of expertise and technology available at VRP. He cites the example of an intramural scientist who originally planned to perform thymectomies on monkeys. After talking with VRP veterinarians and reviewing their facilities, the researcher revised his experimental design and opted for a nuclear-medicine scan and surgical biopsy - a sophisticated approach that yielded more informative data.

Cryopreservation and construction of transgenics are other areas where VRP is helping to keep NIH on the cutting edge of biomedical science. VRP recently expanded the availability of its animal-embryo cyropreservation facilities (see associated article, Mice on Ice), and the program's staff is also currently experimenting with the technology needed to make transgenic pigs.

However, not all the changes on Lang's agenda are high-tech. "We need to enhance communication. Everybody here is busy, so we tend to focus on our own little world. VRP staff needs to be proactive and reach out to investigators," says Lang. Toward that end, the VRP director has asked his staff to go to investigators' labs and meet with them face-to-face whenever possible, rather than just reaching for the phone or firing off an e-mail message. Veterinarians are also being encouraged to attend lab meetings and seminars on topics of projects in which they are involved. "The more we learn about investigators' projects and research areas, the better service we can provide," Lang says.

Comments and suggestions from researchers are another form of communication that Lang wants to encourage. "If they [researchers] have questions or if they have a problem, they should let us know. Sharing information is a crucial part of research," he says. '"If we don't know their concerns or problems, there's nothing we can do about it."

For more information on VRP's services and resources, contact Lang at 496-2527.

Mice on Ice After years of having to turn away NIH researchers who were seeking help with creating and storing of frozen animal embryos, the Veterinary Resource Program's cryopreservation facility is opening its freezer doors to the intramural research community. William Rall, a Ph.D. physiologist who took over the leadership of the Embryo Cyropreservation Program in January, says his facility now has sufficient staff and resources to move beyond the important task of preserving mouse and rat embryos for VRP's National Genetic Resource and start providing similar services to intramural investigators. "We are now able to assist NIH scientists with all aspects of embryo-related services," says Rall. "We are prepared to do whatever is needed to help them, including going to their labs to collect and cryopreserve embryos for storage at VRP or obtaining and breeding the genotype in our animal facilities to produce the embryo-donor females." Embryo cryopreservation, which was first performed in 1973 and which VRP began in the early 1980s, is used for two main purposes: to store infrequently used animal models and to provide insurance against the loss of valuable models that are in constant use. Maintaining models as frozen embryos is a cost-effective way to manage animal models regardless of whether they were produced by conventional breeding or by transgenic or knockout procedures. According to Rall, the cost of cryopreserving a mouse embryo for decades or more has been estimated to be equal to the cost of maintaining the live animal for just one year. Even if a researcher chooses to maintain a small breeding colony of a special animal model, a bank of frozen embryos provides a safety net if the model becomes compromised by genetic changes, disease, or breeding failure. Embryo cryopreservation can also be used along with embryo transfer to eliminate disease that may undermine research projects. Embryos can be collected, washed free of contaminating viruses or microorganisms, and transferred aseptically into a disease-free surrogate mother. Rall notes that the logistical complications that arise from collecting and transferring embryos on the same day can be avoided by cryopreserving the embryos after the washing step and transferring them at a later date. Although a lab might opt to purchase its own liquid nitrogen tanks and other equipment needed for cryopreservation at a cost of about $15,000, Rall warns that the biggest problem is training technicians. "What happens is the lab tech becomes proficient after several months of experience and then leaves," he says. "However, [if] the new tech doesn't know that the liquid nitrogen containers need to be filled, then everything thaws and all is lost." In addition to routine embryo collection, cryopreservation, and storage, the cryopreservation facility staff is available to help NIH researchers with more complex problems. For example, Rall says his group is currently assisting a senior NCI investigator who wants to import a transgenic mouse model from Japan as frozen embryos. Upon arrival at NIH, the embryos will be thawed and transferred into a disease-free surrogate mother. Work is also beginning on the cryopreservation of embryos from guinea pigs and hamsters. - R.K.