Animals are similar to humans in many ways. The muscles of a dog or rat, for example, are similar in physiology and activity to human muscle. By studying muscle function in these animals, we can obtain information that also applies to humans. Animals so used in research are referred to as animal models.
Animal models are an important means of studying diseases as well as normal functions. The animal model must closely mimic the situation we wish to study in humans. Humans are used as subjects in about 30 percent of all biomedical research, but they are not the best research subject when certain problems are studied.
Animal models can be categorized as natural or induced. Natural models are those in which a condition occurs spontaneously, such as atherosclerosis in the squirrel monkey. Atherosclerosis is a prevalent human disease in which fatty deposits occur along the inner walls of the arteries. By studying the natural disease in these monkeys, it is possible to learn facts about the disease that are also true in humans. Other examples of natural animal models are epilepsy in Mongolian gerbils and diabetes in some strains of mice.
Induced animal models are those in which a disease or condition must be artificially produced. Tumor cells, for example, can be injected into animals as a means of studying cancer. Animals may also be treated with chemicals that cause them to develop cancer. Studies of this type showed that certain chemicals in cigarette smoke cause cancer.
Scientists spend a great deal of time developing and selecting appropriate animal models. The most important factor in this decision is that the animal model possesses the biological characteristics that will permit the scientist to answer the research question.
By studying animals that lack one or more parts of the normal immune system, it is possible to gain information about how the total system functions. Immunodeficient animals often make good models of spontaneous or infectious diseases, such as AIDS in humans, and allow researchers to study things like the relationship between the immune system and cancer. In addition, they provide a convenient method of keeping various tumor cell lines alive. For example, human tumor cells can be implanted into a nude mouse without being rejected by the mouse’s immune system, because nude mice lack the immune mechanism responsible for transplant rejection. As a result, the mice act as living (in vivo) culture vehicles for certain tumor cell lines which will not grow properly in a culture flask (in vitro).
Genetic manipulation is probably the most common method for inducing immunodeficiencies in experimental animals. Many different species carrying a wide variety of immune defects are used in specific types of research. The distinct defects include deficiencies in lymphocytes, macrophages, or hematologic factors. Animals carrying less distinctly characterized defects are also available, including those with genetic autoimmune diseases.
The production of animals with specific, genetic immune deficiencies is extremely valuable in understanding the diseases related to hereditary and acquired immune disorders. Immunodeficiencies can be introduced into animal models by means of surgery, genetic manipulation, exposure to chemicals, irradiation, and through induced tolerance. The thymus gland can be removed surgically from newborn mice and rats, thus depriving them of T lymphocytes, cells that attack viruses and tumor cells and that help produce antibodies. Drugs and high-energy radiation are also used in research and medicine to suppress immunity by interfering with antibody synthesis and cellular immune functions.
Animals normally do not initiate an immunologic response (a bodily defense reaction that recognizes an invading substance and produces antibodies specific against that substance) to their own body components. The body learns early in life to differentiate between self and foreign (non-self) substances. Exposing animals to foreign substances at the appropriate time during development makes them tolerant to those substances. This means that subsequent exposure does not result in an immune response. Tolerance differs from induced immunodeficiency in that the immune system is fully functional and capable of responding to other antigens normally.
There are many types of cancers that affect humans and other species, and researchers seek to learn the cause, progression, diagnosis, and treatment for these diseases. Animal models of cancer are generally classified as two types: induced disease and spontaneous disease.
Certain types of cancer have poorly defined causes which scientists wish to understand. For many years it was unclear that cigarette smoking was a major cause of lung cancer. Human population studies indicated a higher incidence of lung cancer in smokers than in nonsmokers, but many arguments were presented in favor of other factors having induced this high incidence of lung cancer. Only after data from animals exposed to cigarette by-products and smoke were carefully compared with data from animals living under the same conditions minus the exposure was it possible to definitely link smoking with lung cancer and warn the public of the health hazards. Many other causes of various types of cancer are under investigation, such as toxin, viruses, and pollutants. Long-term exposure studies similar to those conducted with cigarette smoke are being evaluated in research laboratories.
Some strains of inbred rodents have an unusually high incidence of naturally occurring cancers. For example, more than 80 percent of all AKR mice develop leukemia before the age of one year. Such spontaneous models are useful for evaluating diagnostic and preventive treatments. When testing new treatments or preventive drugs, a group of animals left untreated acts as a control for the study to ensure that the disease develops as expected among the untreated animals. When studying the course, diagnosis, or treatment of cancers, the disease is often induced in a group of laboratory animals to guarantee that the disease progression can be adequately studied. Injection of cancer cells is often used, as is topical application of some cancer-causing chemical directly on the skin or mucous membranes and transplantation of spontaneous tumors. In both spontaneous and induced cancer studies, close observation of the animals under study is necessary. In most studies the size of the tumor or spread of the cancer is evaluated. Rarely is it required that the disease in test animals be allowed to progress to the point that undue suffering or death occurs.