References and resources for this tutorial:
Brenda Griffin and Henry J. Baker, Domestic Cats as Laboratory Animals, Chapter 12 in Laboratory Animal Medicine, 2nd Edition, James G. Fox, et. al., editors (New York: Academic Press, 2002)
A.E. James, The Laboratory Cat, ANZCCART Fact Sheet. This online publication reviews basic information, covering biology, illnesses, anesthesia, handling, nutrition, husbandry and procedures.
Brent J. Martin, The Laboratory Cat, The Laboratory Animal Pocket Reference Series (Boca Raton, CRC Press, 1998)
Sandra McCune, "The Domestic Cat,” Chapter 28 in The UFAW Handbook on the Care and Management of Laboratory Animals, 7th Edition, Volume 1, Trevor Poole Editor, Pauline English Editorial Assistant (Malden: Blackwell Science, Inc., 1999)
Overview
Just as mice and rats are unique in terms of their genetic programming for research use, pigs unique in being a food resource, primates unique in being phylogenetically similar to humans, dogs and cats are unique as research subjects in terms of their history and role as pets. A current trend goes further than calling pets “companion animals,” encouraging the use of the word guardian instead of owner. This history of domesticity makes the cat a useful research animal since they are (for the most part) used to being with people—many technicians and investigators are already familiar with cats in terms of care and handling. On the other hand, the use of cats as research tools is sometimes a challenge in terms of public sympathy since, as with dogs, many people consider them family members.
Felis sylvestris catus, is of the Order Carnivora and the Family Felidae. They are believed to have been domesticated first in ancient Egypt as a result of their ability to decrease rodent populations in grain storage areas. Their history with humans ranges from being worshiped as deities in Egypt to being persecuted as companions to witches in the Middle Ages. Because of their ability as mousers, they were traded widely and introduced into Britain by Romans during the Roman Empire.
Feral cats have always existed at the boundaries of human settlements, tolerated and even supported for their role in reducing rodent populations, eating from handouts or food sources such as garbage dumps. An attempt to control their population over the years has ranged from euthanasia to trap-neuter-release policies such as encouraged by international groups such as Alley Cat Allies. There is continuing controversy over their role in the decrease of small mammals and birds(see Levy comments, Cats and Wildlife and The Effects of Cats on Wildlife), with some citing general habitat loss as the problem and others the favored status of the cat as a protected species due to their popularity. Humane societies have also long been concerned with dealing with the overpopulation of feral cats.
One of the areas of research over the recent past has been that of chemical sterilants for free ranging cats. Research on contraception to control overpopulation currently involves recombinant DNA technology in researching an oral vaccine that would inhibit fertilization:
The problem of controlling the unwanted and feral cat population has now found its way into the research laboratories at Virginia-Maryland Regional College of Veterinary Medicine, where faculty members -- microbiologist Dr. Stephen Boyle and theriogenologist Dr.Beverly Purswell -- are working to develop a feline-specific, oral immunocontraceptive vaccine. (The Alliance for Contraception in Dogs and Cats)
It is interesting to note the wide range of attitudes toward cats, throughout history and in today’s society. They can be seen as pests in need of extermination, useful bodies for high school dissection practice, barn cats to assist in rodent control, part of the multimillion dollar pet business, all the way up to family members for whom kidney transplant surgery is seen as reasonable. There has been a great deal of research done for the sake of cats, due to their popularity as a companion animal. The Cornell Feline Health Center is one such institution, another is The Morris Animal Foundation.
Cats and science
The domestic cat has a long history as a research subject; stray cats were used as research subjects by Claude Bernard and others during the early years of experimental medicine, their small size and availability making them popular candidates for both medical and surgical exploration. They have been used extensively for neurological research, brain and vision studies as well as toxicology. Again, their small size and general tractability when socialized have made them a popular choice as a mammalian model.
Historically, a major use of cats has been for dissection; many high school biology courses and college courses in anatomy and physiology have used a range of animals, frogs, pigs and cats. As with the debate over random source dogs and cats as research subjects, the question of using the large numbers of unwanted stray cats as a dissection resource is another example of the wide range of views about the role of animals. In the 1990s, PETA initiated a public probe into practices at Carolina Biological Supply, a large and well known company, questioning embalming and husbandry procedures. Ultimately, the case brought against them by PETA and the USDA was not supported: see Carolina Biological Supply Wins Case. Increasingly, there are online cat dissection sites such as Anatomically Correct and Online Cat Dissection from McGraw-Hill. Interestingly enough, the ethics of animal dissection in high schools has become a topic in its own right: see Animal Dissection: Where Do You Stand? from the AT&T Educators' Network in Chicago.
Most cats used in research are purpose bred, obtained from USDA licensed vendors; thus they are genetically selected for docility and even temperament. Also, of prime importance, the cats are from colonies specific pathogen free for illnesses cats are susceptible to. This both increases the health status of the animals and cuts down on research variability. Feral cats are not useful behaviorally as research subjects; since they are not domesticated they will be very difficult to handle and highly stressed, again affecting research. Cats that have previously been pets may react adversely to a laboratory environment.
Many feline infectious diseases are chronic infections that may flare up under stress, affecting research being conducted at the time. Vendors producing cats through breeding colonies have the opportunity to eliminate these diseases thereby making available animals free of a potentially significant and uncontrolled experimental variable. Colony control of feline herpes virus has been described. Cats from colonies free of infectious diseases are generally referred to as “specific pathogen-free” or “SPF” cats. SPF cats are generally “barrier-housed.” (Martin, p. 34)
In the last thirty years the number of cats used in research has declined; the total figure given for 1974 was 74,000 while by 1997 the number had declined to a total of 26,091. (From Animal Care Division, USDA as reported by Griffin and Baker, p. 460) Griffin and Baker note,
In fact, cats contribute uniquely to science, and their special biological characteristics and diseases rank them as the favored species for several disciplines, including experimental neurology, some aspects of ophthalmology, retrovirus research, inherited diseases and immunodeficiency diseases. (Griffin and Baker, p. 460)
Cats have been used as models for a number of human diseases. They have been particularly important in research into epilepsy and brain area mapping. They have been historically used in sleep research studies,
Since 1898, cats have also contributed to the study of emotion, cardiac disease, spinal cord injury, cataract surgery, glaucoma, lupus, diabetes, spina bifida and more. Because these and the above diseases are common in cats, these animals stand to benefit greatly from the medical research advances which they make possible. (Partners in Research)
Biology and husbandry
The Animal Welfare Institute’s Comfortable Quarters for Cats in Research Institutions presents an overview of laboratory cat husbandry. Housing for cats varies from single to group housing, usually constructed of stainless steel caging with food and water bowls usually attached to the cage. Cats need to be supplied with a litter box; they prefer some form of clay substrate to dig in and cover their urine and feces; this is normal behavior. The box should be placed away from the food and water dishes to avoid contamination. Cats prefer some sort of raised area for perching and sleeping, away from the food and litter box. Husbandry requirements will necessarily balance sanitation needs with cats’ instinctual need for soft bedding of some sort, with areas for privacy.
When feral, the males tend to be solitary, with the females forming groups with their offspring; the males will tend to remain close by the group, fighting off other males. When the adolescent males reach maturity they will usually leave to form their own group. Once surgically altered, males become sociable; in a laboratory situation, group housing is preferable, or at the least, pair housing. If an individual animal is not compatible with the group, he or she should have some form of visual and even direct contact with other cats. A singly housed cat will need additional interaction with animal care staff. Cats will form social hierarchies and are easily stressed with any changes, thus, moving cats in and out of groups is to be avoided and the housing goal should be one of stability. If group housed, the environment should allow for privacy areas and include multiple feeding, water and litter boxes.
Cats are idiosyncratic individuals who have a high curiosity index; thus enrichment should be part of their normal husbandry. They are predators and any form of enrichment should take this into account. Giving them objects that move or boxes with hidden crevices and openings will encourage natural exercise and reduce stress.
Elevated resting places are particularly favored by cats for watching their surroundings. They also preferred resting places that were warm, dry, and protected on one, or even better, two sides (Smith 1990; Roy 1992) and situated in the corners or edges of an enclosure where they can watch without the possibility of being approached from behind (Roy 1992). A range of resting places should be provided so that cats can choose their degree of contact with other cats. This may be particularly important if they are timid or the focus of aggression. The provision of shelves, ropes and climbing poles (illustrated in Loveridge 1984; Horrocks 1994) enrich the enclosure's vertical complexity and extend the available space. The latest advances in enriched group-housing are illustrated in Loveridge's paper (1994). Shelving allows the available space to be separated into functional areas.(Enriching the Environment of the Laboratory Cat)
Cats are carnivores and easily maintained on commercial diets. Individuals vary in their water intake; canned food will increase drinking, while hard rations include specific water content. They have need for taurine supplementation in the diet; this is usually included in most commercially available food. They prefer the food experienced early in life, are sensitive to taste changes in commercial products, and palatability is increased by food odor. They can develop individual preferences and need variety in the diet.
Many biological variables that exhibit rhythmicity in most mammals have little rhythmicity in the cat. Thus, the cat, when fed ad libitum, eats and drinks randomly throughout the day and night rather than being nocturnal or diurnal (Mugford, 1977; Kane et al., 1981b). Meals are rather small, so the cat normally eats about 8 to 16 meals during a 24-hour period. Even though this appears to be their natural feeding behavior (feral cats eat a wide variety of small prey that include such animals as mice, birds, lizards, insects, etc.), adult cats at maintenance can adapt to being fed only once a day. Growing kittens and pregnant and lactating queens, however, require feeding at more frequent intervals. The relatively short gastrointestinal tract of the cat results in a rapid rate of passage and therefore somewhat lower digestibility for many natural feedstuffs than that of the dog or rat (Kendall et al., 1983). Therefore, high-quality foods best serve this species. (National Academies Press, Nutrient Requirements of Cats, Introduction, p. 1)
Cats may exhibit a wide range of normal blood chemistry panel values, depending on age and sex; writing in The Laboratory Cat, Martin suggests that each institution establish specific perimeters.(Martin, p. 6).
Temperature, humidity, ventilation and lighting
Cats are adaptable, but do best at a temperature range of 64-84 degrees Fahrenheit. Most facilities have a cycle of 12 hours light and 12 hours of dark which is the best for breeding. Although feral cats are largely nocturnal, the domestic cat has adapted. Ventilation must maintain the air quality for the entire room, taking into account cages at the bottom of singly housed racks are used. Ventilation rates of 10-15 air exchanges per hour are normal and necessary to remove the heat and humidity generated by the cats as well as to dilute the particulate contaminants. Humidity should be between 30%-70%. Cats are very sensitive to noise and startle easily. They should be housed away from noisy species such as dogs, pigs or non-human primates. Many report that playing soft radio music lessens their sensitivity to noise and keeps them calmer for procedures.
Monitoring
As with all animals, cats should be observed daily, first at a distance so as to assess their behavior when not disturbed. Grooming is a primary indicator of health and well-being; any cat that looks unkempt should be examined. Other indications of discomfort are listlessness, solitariness and decreased appetite. After examining their behavior from afar, each animal should be checked for any abnormalities. Litter pans should be checked to be sure they are the expected norm for the cat or caging area. Any discharges from eyes or nose should be examined. Any change at all from the normal is an indication for further examination. As cats are easily stressed, particularly by any sort of change, e.g. change in staff personnel, stability should be a husbandry goal. As Martin notes, “Stress also has a wide physiological impact that can affect research results.” (Martin, p. 12)
Illnesses
Cats are susceptible to a range of diseases, some of which are species specific and others which are Zoonotic. (See the Center for Disease Control’s online site, Healthy Pets: Cats). Standard protocols for receiving cats in research institutions may have slight individual differences but will include standard vaccinations, e.g.
Arrival Procedures
Physical examination for immature, aged, ill, or those that fail to meet specific research criteria.
Weigh, sex, identify, and initiate individual health records.
Initiate administration of a broad-spectrum antibiotic for 10-14 days.
Vaccinate for rhinotracheitis (FVR), calicivirus (FCV), and panleukopenia. Feline pneumonitis (FPN) and Chlamydia psittaci may also be given
Provide food and water
(from The Cat in Biomedical Research, lecture notes VSC 443/543, University of Arizona)
Respiratory diseases
Upper Respiratory Disease Syndrome is complex, caused by a variety of viruses and bacteria, Feline Rhinotracheitis Virus,also known as Feline herpesvirus, can become epidemic, particularly under conditions of crowding and stress. Recovered animals, although asymptomatic can continue to shed virus. The illness presents with conjunctivitis, sneezing, eye and nose discharges, usually with decreased or no appetite (cats that are unable to smell their food will usually not eat) and fever.
Viral diseases
It is also standard to test their status for two major retroviral illnesses, Feline Leukemia Virus (FeLV) and Feline Immunodeficiency Virus (FIV). Both diseases are contagious and fatal to cats. The FeLV virus is shed in body secretions and is short lived outside the body; close proximity, grooming and shared litter pans lead to it being quite contagious. The FIV virus is more difficult to spread, the usual route is via a bite and thus FIV tends to be a disease of free-roaming unaltered male cats. Feline Infectious Peritonitis (FIP) is another contagious and fatal disease, caused by a coronavirus, with a variable presentation, ranging from sub-clinical to severe debilitation. It can present either as the effusive form (fluid accumulation in the abdomen and other body cavities) or the dry form (characterized by pyogranulomatous lesion in organs or organ systems). Panleukopenia, or cat distemper, can be a fulminating disease for kittens. It presents with lethargy, fever and anorexia.
On occasion, if group housed, fights can flare up and the resulting bites and scratches under the surface of the skin may abscess; Pasteurella multocida may colonize the wound. The main treatment is providing open drainage for the wound.
Feline urological syndrome (FUS)
This is a multifactorial disease with dietary, behavioral and psychological components. Cats can develop a build up of mineral concentrations in the urinary tract, also known as urolithiasis. This can lead to bladder inflammations and blood in the urine and in serve cases, particularly male cats, the small crystals can block the urethra. This is a veterinary emergency. Cats should be monitored several times a day and the litter pans checked for urine; any cat seen to be experiencing any pain or discomfort on urination should be immediately examined. A cat with this syndrome will make frequent unsuccessful trips to the litter box, often crying out with pain. Cystitis, with accompanying symptoms of blood in the urine and frequent urination is also cause for immediate veterinary exam.
Parasitic diseases
A typical conditioning protocol for cats will include treatments against ear mites (Otodectes cynotis), fleas (Ctenocephalides felis) and intestinal parasites such as tapeworms, roundworms, giardiasis (a protozoan illness), and toxoplasmososis.
Handling and Procedures
The University of Minnesota has information and pictures about Restraint and Handling of Animals, scroll through the species until you reach the section on cats. Minimal restraint is best for cats as is the familiarity of staff working with them. For some timid or more aggressive cats, wrapping them in towels can be helpful, as is the use of a cat bag. Highly stressed cats are difficult to handle; if restraint for a procedure is necessary only trained staff should handle the animal. Again, this is a strong reason for obtaining cats from established vendors because they will be genetically selected for docility and be well used to laboratory procedures. Cat bites can cause serious inflammatory response in people:
Cats frequently carry Pasteurella multocida in their mouth secretions. Since cats tend to cause puncture wounds on hands near joints during bite incidents, serious joint infection or general body infection can result from Pasteurella. The zoonotic agent Bartonella henselae causes human Cat-Scratch Fever. This rickettsial organism enters the body through scratch wounds resulting from improper handling of cats. During primary infection, symptoms include fevers that come and go. Life-threatening conditions can develop in those persons with compromised immune systems, such as those with HIV infection. A recent survey indicated that 40% of pet cats examined had blood cultures positive for Bartonella. Cats received in Princeton University facilities are not tested or screened for Bartonella, so it is important that you treat all cats as if positive. (Zoonosis, from Princeton University, Health and Safety for Animal Care Workers website)
Another zoonotic disease, toxoplasmosis, is of special concern to pregnant women or immuno-compromised individuals.
Current research using cats
Cats are often the model of choice for neurological research, as well as studies on hearing, balance, movement and motor neuron research related to spinal cord injury. Due to anatomical similarities in brain structure they have been used for mapping studies.
They have a particularly valued place as models for viral disease syndromes since both Feline Leukemia Virus (FeLV) and Feline Immunodeficiency Virus (FIV) have similarities to human viral syndromes.
Thus the FIV virus infection in cats has been used as a model of AIDS for research. FIV research originally had the goal to develop both a better understanding of the disease process as well as a vaccine for cats (see UF Researcher Develops AIDS vaccine for cats); here is an example of how general research resulted in two divergent directions in applied work, benefiting both cats and people.
Another infectious disease that cats are susceptible to, Helicobacter felis, is a degenerative disease affecting the gastric mucosa. Current research has identified Helicobacter pylori, as a prime factor in human gastritis, ulcers and stomach cancers. A mouse model of Helicobacter disease, using a naturally occurring mouse model and biotechnology, is combined with the genomic knowledge of mice, cats and humans. The feline model for Helicobacter disease is part of this inter-species picture.
Increasingly, the genetic mapping developments for different species and the biotechnological explosion join forces. The Development of the Domestic Cat as a Model for Genetic Analysis focuses on a number of diseases and syndromes naturally occurring in the cat that have relevance to humans. The Cat Genome Project, located at the National Cancer Institute, “focuses on development of the cat as an animal model for human hereditary disease, infectious disease, genome evolution, comparative research initiatives within the family Felidae, and forensic potential.” The National Cancer Institute’s Laboratory of Genomic Diversity has worked on the feline genome.
The Cat Genome Project, which relies on contributions from other scientists as well as those in his lab, is a comprehensive genetic analysis of Felis catus, a.k.a. the common house cat, one of 37 cat species. (Obtaining DNA requires no more than a blood or saliva sample, O’Brien points out.) Analyzing the cat genome has already yielded insight into puzzling human diseases. House cats suffer from 200 genetically inherited disorders that also afflict people—including muscular dystrophy, polycystic kidney disorder and retinal degeneration—and scientists have pinpointed the specific genes in cats responsible for nine of these disorders. But the most striking disease research in O’Brien’s lab concerns AIDS. (Happening Cats).
Another area of research, not focused on biomedical applications to humans are the many ongoing molecular biology studies aimed at conservation of species for the larger, wild cat species: see, for example, The Feline Research Program, Texas A&M University, or Wild Clouded Leopard Research or LiFeline research from Belize.
Further resources
Cat links from NetVet/Electronic Zoo
The Cat in Biomedical Research: VSC 443/543, detailed lecture notes from the University of Arizona
Husbandry Manual for Small Felids
Study question
1. Due to their status as pets, the use of cats as research subjects has often sparked particular controversy. Do you think this status should have an influence on their use as subjects? Why or why not?
2. Currently, there is research into creating a genetically modified cat that would lack the protein that many people are allergic to. See the online article, Designer Cat Controversy. Do you think this research should go forward? Why or why not?
Discussion question:
The population of stray and/or feral cats has historically served as a resource for businesses processing animals for dissection practice. Shelters have been able to add to their funds by selling cats, both dead and alive to processing companies. Those opposed to the practice say that shelters should be seen as safe havens by the public; others disagree, saying that if animals are to be euthanized, they should at least serve some educational purpose. Looking over two anti-dissection sites, School Labs, from the HSUS and an online cost-comparison discussion from the Physicians Committee for Responsible Medicine as well as materials from Carolina Biological Supply and But the Cat Came Back, do you think that stray/feral cats should be made available for dissection? Why or why not? What role do you think the public should have in deciding this?
Another resource on this question, which discusses the issue of dissection of frogs in high schools, is "The Jenifer Graham Case" in The Human Use of Animals: Case Studies in Ethical Choice, F. Barbara Orlans, et. al. (New York: Oxford University Press, 1998).