Small Companion Animals:

From the Lap to the Lab

By John McArdle, Ph.D.

AV Magazine Spring 2001, Small Companion Animals

If one examines the historical development of laboratory animal-based experimentation and current United States animal welfare laws, the interconnectedness between those species of animals kept as human companions and those deemed appropriate for research, testing, and educational demonstrations is a recurring theme. It is not uncommon to find individual investigators who cause pain and distress to one of their laboratory animals and go home to play with another representative of the same species. Purpose-bred laboratory animals are a relatively recent development in biomedical research and testing. For the first few centuries only wild animals, domestic livestock, and "pets" were available for use by experimental biologists. For example, guinea pigs were originally domesticated in South America as a food source. In the 16th century they were being distributed throughout Europe and commercially bred as fancy pets. It was not until the late 18th century that Levoisier used them in his experiments on heat production. During the next two hundred years, guinea pigs gradually became one of the most common non-rodent (yes, they are not rodents) species used in modern laboratories.

Feral rodents (rats and mice) have always been readily available, with the first records of research (mice) beginning in the 1600s. It was not, however, until the early 20th century that consistent efforts began to produce standardized laboratory-bred rodents; and not until the late 1940s that this became the major breeding industry found today, where such animals are produced by the millions every year.

In many cases, however, the worst atrocities committed in the name of early experimental science (i.e., the work of individuals such as Claude Bernard and Francois Magendie) were reserved for our closest animal companions—cats and dogs. Again, these animals were viewed as a readily available, easily exploited resource, rather than the species with which we most often share our homes.

Initially cats and dogs might be acquired through purchases from individuals with dubious or entirely lacking evidence of prior ownership of the animals. Even such luminaries of the animal research community as Frederick Banting (co-discoverer of insulin) have long been suspected of simply going out to the streets of Toronto to steal whatever dogs were needed for their experiments. In the United States a different and socially more damaging solution to the problem of supply and demand of laboratory animals was created.

Basic and applied animal experimentation increased significantly during the Second World War to deal with pressing clinical and military concerns. After the war, large numbers of soldiers returned to the United States, entered colleges and universities, and acquired advanced degrees, many of which were in areas of biomedical research that traditionally utilized laboratory animals. To meet this new demand, companies developed procedures for the large-scale production of genetically purified, pathogen-free, unnaturally uniform laboratory rodents. Henry Foster, founder of the Charles River Breeding Laboratories, was one of the first principal players in the field. His company is now the largest breeder in the world, producing millions of animals every year.

However, the initial shortage of animals needed to be filled quickly. In the United States the research community noted that throughout the country local animal shelters had significant "surplus" cats and dogs. Thus began the concept of pound seizure, the literal legal requirement that local refuges for homeless companion animals must, on demand, provide animals to research facilities and universities. Although once widespread, this reprehensible practice is gradually being eliminated from the country, in large part due to the massive expansion of purpose-bred laboratory animal producers and the concerted efforts of local, state, and national animal advocacy organizations dedicated to defending the rights of these two companion animal species.

This dichotomy of public and regulatory attitudes on protecting laboratory animals is also reflected in the enforcement provisions of the Animal Welfare Act (AWA). One of the principal factors influencing the initial passage of the AWA was the theft of a dog that was sold for use in a research laboratory. Subsequent amendments of the act clearly state that its requirements applied to all "warm-blooded animals, as the secretary may determine is being used or is intended for use for research, testing, experimentation, or exhibition." Such unambiguous Congressional instructions were somehow translated by the USDA into a new form of vertebrate taxonomy. According to the USDA, the only species requiring legal protection were cats, dogs, guinea pigs, rabbits, hamsters, non-human primates, and a few others. The vast majority (now more than 95 percent) of animals (rats and mice) consumed in the designated activity areas were excluded. It is clear that the USDA chose to include those species it believed had more public sympathy, rather than providing uniform rules and protection for all laboratory animals. It has taken more than 30 years to correct such a gross taxonomic error and the legal and regulatory neglect it fostered. This is not what Congress intended and certainly not what the general public expects from the nation's most important piece of animal protection law.

Readers interested in a review of the uses of rats and mice are referred to the spring 1998 issue of the AV Magazine. What follows is a brief overview, with examples, of how the USDA "listed" small species of common companion animals are used in research and testing.

Guinea Pigs

As mini-livestock, guinea pigs are still common in areas of Argentina, Brazil, Uruguay, and adjacent countries. Their status as small companion animals extends worldwide. Within U.S. laboratories they continue to be used in significant numbers to investigate such topics as the impact of cigarette smoke, repair of spinal cord injuries, tuberculosis, multiple aspects of the auditory system, effects of alcohol on the heart, kidney function, characteristics of osteoarthritis (especially in the knee), nutrition, genetics, infectious diseases, reproductive biology (especially endocrine control of human pregnancy), and several types of toxicity/safety tests.

Although small and very distantly related to humans, guinea pigs have not escaped selection as surrogates for a variety of human problems. In New York investigators are trying to examine "oxidative and other damage produced in the pulmonary system of guinea pigs by exposure to cigarette smoke, and to determine the effects of dietary vitamins C and E on the process.” Despite decades of animal experiments based on chronic, forced exposure to tobacco smoke and a Finnish human epidemiological study examining use of antioxidants by smokers, these researchers claim that these new experiments will be "the first to comprehensively characterize oxidative damage due to cigarette smoke" and "furnish additional strong rationale for dietary antioxidant vitamin recommendations to those [human] smokers who are unable to quit." Apparently, these individuals believe that what is good or bad for guinea pigs can be directly applied to humans, disregarding tens of millions of years of evolutionary separation and distinction.

In Alabama, investigators are exposing guinea pigs to 10 percent ethanol for a period of six weeks and then examining their hearts to see if such treatment provides any protective benefits from heart attack-like manipulations. They claim this knowledge will have direct applications in "the clinical arena.”

Scientists in New Jersey have constructed a complex environment in which guinea pigs are allowed to freely move about. Different aspects of the composition and distribution of their food will be varied and the impact of these changes in foraging and eating behaviors will be quantified. Although these animals will inhabit a more diverse and enjoyable laboratory setting than do their brethren at traditional facilities, it seems unlikely that the data collected will provide the knowledge needed for "a complete analysis of human feeding and regulation and their associated disorders."

Researchers at the Oregon Health Sciences University are exposing guinea pigs to morphine to understand human gender differences in reward and homeostasis; and to marijuana chemicals to examine their effect on the secretion of major reproductive hormones. Neither of these studies offers biologically convincing justifications for turning guinea pigs into surrogate human junkies.

Although not the workhorses of the toxicology industry, guinea pigs have been used in significant numbers in a variety of potentially painful and distressful testing protocols. These have ranged from the old immersion test in which these animals are repeatedly placed for four hours in containers of test substances; to primary skin irritation tests where materials are directly applied to abraded areas of the animals' skin.

Guinea pigs are also used to test for photoallergic reactions and skin sensitization. In the former animals are systematically given test materials for 10 to 14 days and then exposed to specific wavelengths of light on a patch of shaved skin. For the latter the animals are treated (sensitized) in such a way as to build up an immunity to a test substance to which they are later exposed to elicit an immune reaction. There are seven different versions of this test and at least one in vivo alternative that uses mice rather than guinea pigs.

In a related procedure, guinea pigs are sensitized to specific compounds and later exposed to determine if an antigen (anaphylactic) response is possible. When positive, the animals experience scratching, coughing, labored breathing, retching, cyanosis or death.

Hamsters

Although long associated with the pet trade as small, cuddly companion animals, hamsters are extensively used as laboratory animals. The most common type of hamsters (Syrian) encountered today, whether at home or in a lab, are all descendants of three or four littermates that were captured and exported from their natural habitat near Aleppo, Syria in 1930. Striped, Chinese, European, Djungarian, and Armenian are all less commonly utilized types of hamsters.

Because hamsters are a legally protected species, there is information on the extent of their use in the United States, with more than 200,000 utilized annually in laboratories. Nearly one-quarter of these are subjected to experimental or testing procedures that involve pain and distress that are not alleviated by either anesthetics or analgesics. Another quarter are parts of painful studies for which such relief is provided.

The range of diversity of research projects involving hamsters is impressive. A major focus of experimental activity looks at such sensory systems as taste and vision. They are also utilized as induced models for cardiopulmonary, inflammatory, and neoplastic diseases; cardiomyopathy, estrogen-induced carcinogenesis; drug and carcinogen metabolism; muscular dystrophy therapy; aging; asthma; pancreatic cancer; prion-type (mad cow) diseases; and various aspects of natural/ artificial biorhythms.

Two specific examples show how removed from reality hamster experiments can become. Like any species that inhabits seasonally difficult environments, hamsters evolved the ability to periodically increase body fat reserves, which are then utilized during times of the year when food resources are rare or absent. This is much like when chipmunks who bulk-up before long Minnesota winters. Such repeated cycles of weight gain and loss are a natural adaptation to specific environmental situations. They have absolutely nothing to do with human obesity or its causes, which are primarily psychological rather than any type of human dietary adaptation.

This simple fact of natural history is being ignored by researchers at Georgia State University, who insist that hamster seasonal weight gain is a valid model for human permanent obesity. They further suggest that by identifying the specific physiological and neurological mechanisms employed by hamsters to meet their dietary needs (none of which are relevant to humans—past or present), obese humans may be helped.

Although the biomedical hysteria and media hype designed to encourage acceptance of xenotransplantation (involving the use of primate or pig organs in human patients) is subsiding as the obvious dangers of such procedures and apparent lack of necessity become better documented and more widely known, the least justifiable xeno-related animal experiments continue to receive government funding. Rodent models for xenotransplantation have been widely criticized for their lack of relevance to human clinical concerns and the false sense of potential success they produce (i.e., rejection-related phenomena are less drastic in rodents). However, this has not stopped researchers from including hamsters among the species subjected to such apparently useless experimental manipulations.

Rabbits

Rabbits, mostly albino New Zealand Whites, are widely used in both research and testing as well as the production of certain types of biological compounds called polyclonal antibodies. For decades these animals were routinely used for the production of all antibodies used in basic research laboratories. Due to developments in the in vitro production of monoclonal antibodies and use of chicken eggs to produce polyclonals, it is becoming increasingly difficult to justify the use of rabbits for such purposes.

Within the biomedical research laboratories, rabbits are currently used for studies of epilepsy, diabetes and atherogenesis, induced lupus, the auditory system, orthopedics (emphasis on joints and tendons), various types of brain lesions, hemorrhagic colitis, development of the heart, and exposure to narcotics.

For example, researchers in Philadelphia are exposing pregnant rabbits to cocaine to determine the long-term effects this has on subsequent behavioral development after birth. The experiments involve traditional avoidance behavior and locomotor responses and a claim that drug therapies will be tested in an attempt to reverse or lessen the consequences of prenatal exposure of rabbits to cocaine. Although this project may be of interest to any lagomorph cocaine addicts prowling around urban and rural yards and fields, it is unlikely to "offer therapeutic approaches for restoring brain function" in human infants whose mothers used cocaine while pregnant. Interestingly, this project was conducted by a researcher named Harvey.

Due to "a resurgence of interest in marijuana for medicinal purposes,” a researcher in Georgia is using rabbits to develop a method for delivering the pharmacological benefits of the active ingredient. Rather than smoke marijuana, he is working on a means to apply it directly to the patients' eyes. Surprisingly, an earlier project on this same approach, which was tried on rabbits, dogs, cats, and monkeys, failed to work with humans.

Rabbits have developed a system of induced ovulation that significantly increases their chances of successful fertilization and pregnancy. Although the human reproductive system has no counterparts to the above, this has not stopped researchers in Oregon from manipulating, quantifying, and mutilating the brains of rabbits in order to better understand "neurologically related infertility" in humans.

Researchers in Los Angeles have developed a rabbit model of Lyme Disease with "local and disseminated disease manifestations similar to those in human infections." Although natural history studies have not indicated that Lyme Disease is a serious or minor problem for natural populations of rabbits, this artificially induced version will, the investigators claim, "contribute toward our understanding of chronicity in humans."

A project in Illinois plans to examine the factors involved in diagnostic ultrasound damage to lungs. The description of the project clearly states that in terms of critical morphological features of the lungs, rabbits and humans are in entirely different, unrelated groups. This has not, however, stopped this investigator from exposing the former to varying degrees of lung damage.

For the past few decades, the use and abuse of rabbits in toxicology testing has been extensively documented, criticized and, in a few cases, replaced by alternatives. Some of these procedures, such as the Draize eye and skin tests are very familiar to animal advocates, being the focus of prolonged campaigns to bring about their demise. Others such as pyrogen testing may be less well known. What these three have in common is the existence of humane replacement alternatives that are either available now or soon will be.

Conclusion

Getting small companion animals out of biomedical research laboratories will require a concerted effort to educate scientists, funders, health-related charities and the general public on the lack of biological and clinical validity for such animal models. There may then come a time when these "friends" will be found only in our homes and not on annual summary forms of pain and distress.

Removing rabbits from toxicology testing laboratories is a realistic, achievable goal towards which significant progress has been made. Although it may take longer, this same scenario applies to the use of rabbits in photoallergic reaction, reproductive toxicology and teratogenicity testing, and to the various tests for which other small companion animals are now subjected. The steps to be followed towards accomplishing these goals are underway by both animal advocates (individually and through organizations) and the scientists who are developing, validating and promoting the use of humane alternatives to replace all of the animal-based procedures that can be defended only by invoking tradition, since none of them ever passed the same vigorous validation procedures currently required of alternatives.

McArdle, John, Ph.D. (Spring 2001). AV Magazine. Pages 2-6.

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