OVERVIEW OF ANIMALS IN RESEARCH

  1. Introduction

    Research is performed on live subjects in many ways

    1. Humans versus animals

      Humans value themselves more than animals, hence research gets done on animals more than humans.

    2. Some humans versus others

      In some circumstances, research is performed on humans. Examples include experiments performed in NAZI concentration camps(inhumane), studies with military personel (vaccination trials), or experiments on consenting adults.

    3. Experiments versus Epidemiology

      Epidemiology studies the development of disease, or drug efficacy in the natural population, or in animals doing their normal work. Examples include studies that follow groups of people over several years to monitor the development of particular diseases, or studying animals at the farm, in barns, in kennels or at the race-track. An experiment involves research in the lab under controlled, artificial conditions.

  2. Therapeutic testing and development

    Animals have played a major role in drug and vaccine development

    1. Jenner and milkers nodules

      Edward Jenner discovered a vaccine against small pox after observing that women who received cow pox (milkers nodules) from cows were resistant to small pox.

    2. Diptheria - horse serum

      Horses provided the early antisera against diphtheria

    3. Poliomyelitis - rabbits, monkeys and rodents vaccine development

      All these species played a role in developing the polio vaccine

    4. Lithium - rats, guinea pigs

      Lithium carbonate is an antidepressant

    5. Librium - cats

      So is Librium

    6. AIDS

      Many animals used in therapeutic testing of new AIDS drugs

    7. Psychoactive drugs

      Ketamine was developed in cats as an anesthetic for humans. Now it's the standard cat anesthetic

    8. Hormone replacement

      Horses supply for postmenopausal women (controversial).

    9. Gene therapy

      Mice have been used most to develop the ability to alter genetic defects.

    10. Surgical techniques

      Sheep used to develop heart transplant techniques, dogs used to develop artificial hip surgery.

  3. Human disease

    Animals often have similarities with humans which make them good models for studying human disease.

    1. Some animals are like humans in some ways

      1. Mice

        MIce are the basic mammal used in research, and have many broad similarities with all mammals, including humans.

      2. Pigs

        In many aspects of metabolism pigs have surprising simiularites with humans. (Of course, some humans have similarities to pigs, usually our roomates.)

      3. Guinea pigs

        Same kind of placental attachment as humans (hemochorial)

      4. Primates

        The group of animals most similar to humans. Rhesus monkeys are used extensively in research.

    2. Nutritional deficiencies

      1. Beriberi

        Vitamin B1 deficiency

      2. Rickets

        A deficiency of bone development due to lack of calcium or vitamin D.

    3. Endocrine disorders - Dogs

      Dogs played a major role in research on these endocrine diseases

      1. Diabetes

        Insulin deficiency

      2. Hypothyroidism

        Low thyroxine

      3. Addison's disease

        Cannot control salt balance

    4. Neoplasia - Mice

      Mice are used extensively in biomedical research

      1. The coat color connection

        Clarence Cook Little, founder of the Jackson Laboratory, who originally bred mice for show, noticed that certain tumors appeared in inbred mice of certain colors. This led to the use of inbred mice being used in cancer research.

    5. Immunology

      1. SCID mice

        Severe Combined Immumodeficiency Mice lack B and T cells.

      2. Nude mice

        Nude mice lack a thymus (athymic) and therefore don't have T Cells.

      3. Knock out mice

        Have specific genes deleted

      4. Transgenic mice

        have specific genes inserted

      5. Horses

        Horses have been used as models of exercise induced stress to determine if such stress suppresses the immune system.

    6. Infectious disease

      1. Cytomegalovirus in guinea pigs

        Cytomegalovirus is an important infection of the unborn child. Because the guinea pig has a placenta similar to humans it is used as a model to study CMV infection.

      2. Retroviral diseases - SIV, FIV, BIV, BLV, EIA, OPP, CAEV

        Retroviruses of animals are related to the Human Immunodeficiency Virus. These viruses may induce cancer by a process known as malignant transformation, or they may cause immunodeficiencies and/ or slow wasting diseases. The following are common retroviral diseases of animals and sometimes used as models to study HIV:

        1. SIV = Simian Immunodeficiency Virus - Monkeys
        2. FIV = Feline Immunodeficiency Virus - Cats
        3. FeLV = Feline Leukemia Virus - Cats
        4. BIV = Bovine immunodeficiency virus - Cattle
        5. BLV = Bovine Leukemia Virus - Cattle
        6. EIA = Equine Infectious Anemia- Horses
        7. OPP = Ovine Progressive Pneumonia (Visna virus) - Sheep
        8. CAEV = Caprine Arthritis and Encephalitis Virus - Goats

      3. Bacterial diseases - protection or virulence studies in mice

        MIce have been used extensively to test the ability of various bacteria to cause disease

    7. Antibody production

      1. Monoclonal antibodies

        MIce are used extensively in the production of monoclonal antibodies.

  4. Animal disease

    Animals are used directly in diseases of animals.

    1. Direct relevance

      It can be difficult to justify the use of a mouse, say, for the study of human disease. However, in veterinary medicine it is possible to study the disease directly in the species affected.

    2. Writing grants

      Some people will say that a particular animal disease is also a good model for human disease, in order to make a grant more likely to be funded.

    3. Disease of the species versus disease of the breed

      Sometimes breeds of animals have particular diseases which do not apply to the rest of that species. This is usually a result of inbreeding.

      1. Horses

        Combined Immunodeficiency is a genetic disease of Arabian horses.

      2. Miniature pigs

        Different requirements than large pigs

      3. Beagles

        The model research dog, but does not have diseases of some other dogs

      4. Dalmations

        Dalmations are prone to deafness

      5. Collies

        Collies are prone to particular eye problems

      6. Bedlington terriers

        Bedlington terriers are prone to copper storage disease of the liver.

  5. Review Questions

    1. Which of the following is an animal experiment, and which is an epidemiologic study? A survey of racehorses at the track in which the risk factors for traumatic leg injury are studied. Running 10 horses on a treadmill at different speeds to determine the effect of stress on equine immune function. The use of pigs to elucidate cholesterol metabolism in humans. The following of 2000 professional men to determine what lifestyle factors contribute to heart disease.

    2. You should understand how animals contribute to therapeutic testing and development in each of the examples given in the notes.

    3. Briefly explain in what way mice, pigs, guinea pigs and primates are each useful as models in biomedical research. In what way is their use limited?

    4. What are Beriberi and Rickets?

    5. Why are dogs valuable in the study of diabetes?

    6. Why are mice so extensively used in Cancer research? What is the coat color connection?

    7. Explain what SCID, nude, athymic, knockout and transgenic mice are.

    8. Why are guinea pigs useful in cytomegalovirus research?

    9. What do SIV, FIV, BIV, BLV, EIA, OPP and CAEV stand for. What is their significance in infectious disease research of humans?

    10. What is a monoclonal antibody? How are they produced (in simple terms).

    11. In writing grants to study animal diseases, what "trick" do researchers commonly employ to increase the chance of having their grant funded?

    12. Why might a beagle not be appropriate for research in all diseases of dogs?