Principles of Animal Research for Graduate and Undergraduate Students

Mark A. Suckow,Kay Stewart

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128023662
• Topic: Psychologie
• Subtopic: Neuropsychologie

Principles of Animal Research is the first publication to offer a broad look at animal research science for a student, early researcher, or technician. Offering guidance for all aspects of the research experience, including the research and development of a thesis, model selection, experimental design, IACUC protocol preparation, and animal husbandry and technical procedural needs, the book is a necessary addition to every student, technician, and researcher's education.

• Provides background material for students to understand the broader backdrop against which animal research is undertaken
• Includes ethical and regulatory information
• Covers commonly used animal models and the process to choose a model for biomedical research

Chapter 1

Brief Historical Overview on the Use of Animals in Research

M.A. Suckow¹, and K.L. Stewart^{2 1}University of Minnesota, Minneapolis, MN, United States ²University of Notre Dame, Notre Dame, IN, United States

Abstract

The relationship between animals and man has evolved over several millennia and it is now recognized that a multitude of biological similarities allow us to use animals as models to better understand basic biological, physiological, and pathological processes with import to both human and animal health. A great deal has been learned from animals that spontaneously develop disease, as well as from new models that have been genetically manipulated. An appreciation for the importance to control animal care variables that might affect the integrity of research, as well as a desire to optimize animal health and wellbeing has led to development of standards for animal care and evolution in approaches to ensuring a sound environment for animal maintenance.

Keywords

Animal care; Animal care panel; Animal models; Comparative medicine; Guide for the Care and Use of Laboratory Animals; History

Chapter Outline

1.1 Introduction

1.2 Early Attitudes Toward Animal Health and Disease

1.2.1 Early Relationship of Man With Animals

1.2.2 Animal Disease as a Way to Learn About Human Disease

1.3 Development and Emergence of New Animal Models

1.4 Improvements in Approaches to Animal Care

1.4.1 Cages

1.4.2 Food and Water

1.4.3 Environmental Parameters

1.5 Summary

References

1.1. Introduction

Animals play significant and varied roles in our lives, often to our benefit though sometimes to our disadvantage. For example, pet animals serve as loyal companions; some animals provide entertainment, such as a dog retrieving a tossed object; some perform work, such as herding, guarding, or retrieving; and some provide food. In contrast, our interactions with animals are sometimes viewed as negative, such as with verminous rodents or aggressive animals that inflict injury. Nonetheless, the animal kingdom has developed an overall close, often symbiotic, relationship with man.

One particular way in which the existence of man and animals has intersected is the use of animals as research and teaching subjects. The advancement of knowledge through the use of animals has benefited both human and animal health through scientific inquiry. It is widely understood that while differences do exist and there is no perfect model, extrapolation of knowledge learned from animal studies can be used to better understand the physiology, anatomy, and disease processes of man. This chapter will explore how the particular relationship between man and animals as research subjects has developed over time.

1.2. Early Attitudes Toward Animal Health and Disease

Proper perspective of early attitudes requires some understanding of current thinking. The idea that animals represent sound models which allow researchers to gain insight into basic principles of biology and medicine and which can be applied to solving problems of mankind is widely accepted by the scientific community. Underlying this principle is recognition that basic biologic processes and disease processes are similar, though not necessarily identical, between animals and humans, thus supporting the thinking that animals can serve as research models. The term, comparative medicine, refers to the study of phenomena that are basic to diseases of all species. Similarly, the term zoobiquity is sometimes used to describe the idea that humans and animals get many of the same diseases and that communication and interaction between those specializing in human and animal health should logically yield synergy and benefit for both man and animals.

1.2.1. Early Relationship of Man With Animals

At approximately 20,000–15,000 BC, man changed from being strictly a vegetarian to a nomadic hunter. The relationship of man as the hunter and animals as prey slowly evolved to incorporate symbiosis with some animals. For example, gradually man would share the kill of dog packs and eventually began hunting in unison with dogs. This relationship led to domestication of dogs and later domestication and husbandry of sheep, goats, and cattle by 3000 BC. Over time, domestication and animal husbandry became an established part of civilization. That animals are susceptible to disease was noted early, as plagues often decimated domesticated animal populations, thus impacting humans who depended on livestock for food and labor (Wilkinson, 2005).

The early philosophers weighed in on the relationship of man to the animal kingdom with varied opinions and perspectives. Plato had a rather low opinion of the animal world and discouraged any sort of comparison between man and animals (Wilkinson, 2005). In contrast, Celsus and Galen both used animals to better understand anatomy and physiology as it might relate to man, with Galen using a variety of species, including mice, sheep, pigs, dogs, weasels, bears, and on one occasion an elephant.

1.2.2. Animal Disease as a Way to Learn About Human Disease

In the fifth century, AD, Vegetius recorded observations and thoughts with respect to the care of domestic animals, including the care of cattle and horses ill with infectious disease, such as the viral disease, rinderpest and the bacterial disease, strangles. This was driven in no small part by the economic importance of these species at that time. Sometimes referred to as the “Veterinary Hippocrates,” Vegetius postulated the idea that much disease was the result of transmitted contagion; that is infectious agents. This was in contrast to the widely held belief that such illness in animals was the result of divine displeasure. From this idea arose methods to control infectious disease of animals via isolation and it was not long before comparisons were made to similar diseases in humans.

In the mid-13th century, Albertus Magnus wrote De animalibus, a treatise that discussed human and animal diseases together, and postulated ideas related to transmission of animal diseases; that is, they might be transmitted via bite; via contact with a diseased animal; or via air respired from a sick animal. These ideas led to further unification of theories underlying diseases of animals and man.

The application of the principles of isolation as an approach to control infectious disease in both man and animals continued and gained importance throughout Europe. In 1775, having successfully led an effort in France to control a rinderpest outbreak in cattle, Fèlix Vicq d’ Azyr expressed the idea that just as there is a great deal to be learned about man through comparative anatomy, there is also a great deal to be learned from “comparative medicine.” In this way, then, d’ Azyr first articulated the idea that animals could be used to systematically study diseases with import to man. Further, d’ Azyr believed that, given the unity of human and animal medicine, animals could be used to conduct important experiments that would be considered criminal if conducted in humans.

Over time, animals came to be seen as important tools in efforts to more clearly understand diseases affecting man. Early efforts focused on the study of infectious disease. For example, in the 1800s, Francois Magendie studied the transmission of rabies, first by inoculation of saliva from an affected human to a dog. Investigations by others into “wool sorter's disease,” now referred to as anthrax, used rabbits, suckling pigs, guinea pigs, as well as dogs, to establish a transmissible, bacterial agent as the cause of the disease.

In 1901, John D. Rockefeller established the Rockefeller Institute for Medical Research in New York. The underlying idea was to link scientific research to clinical teaching within a medical school. Interestingly, the public was encouraged at that time to bring sick animals to the Institute for evaluation. In 1910, a Plymouth Rock hen was brought to the Institute and came to the attention of Dr. Peyton Rous, a physician. Subsequent work resulted in isolation of the first retrovirus and led to Rous being awarded the Nobel Prize in Medicine in 1966.

By the mid-20th century, the idea that animals can serve as important models to understand the basis of human disease and to develop treatments became an accepted part of scientific practice. Even today, concepts that are developed through the use of nonanimal technologies, such as molecular biology, are frequently evaluated in animals to establish validity in an organismic system. This is especially true for technologies that are hoped to be used as treatments for disease in humans, since animal testing is typically required before any evaluation in humans can begin.

1.3. Development and Emergence of New Animal Models

As the use of animals as research subjects became a more common and standard part of the scientific process, the animals used became somewhat more standardized. For their small size, relative ease of maintenance, high fecundity, and relatively short lifespan mice and rats emerged as the species that were most commonly used. Systematic breeding of rodents led to inbred strains of animals with specific, defined characteristics that could be leveraged for some types of inquiry. For example, the Brattleboro rat was developed at a private research laboratory in West Brattleboro, Vermont when an astute animal care assistant noticed that drinking bottles attached to one cage among hundreds of Long-Evans rats were nearly always empty. Upon learning of this observation, the scientist in charge of the rats recognized the importance of the discovery bred animals from this particular line and developed them as an animal model of diabetes insipidus, an important human disease involving hypothalamic co...