Animal Models for the Study of Human Disease

P. Michael Conn, P. Michael Conn

• Editorial: Academic Press
• Año: 2013
• ISBN:
  9780124159129
• Categoría: Scienze biologiche
• Categoría: Fisiologia

Animal Models for the Study of Human Disease identifies important animal models and assesses the advantages and disadvantages of each model for the study of human disease. Thefirst section addresses how to locate resources, animal alternatives, animal ethics and related issues, much needed information for researchers across the biological sciences and biomedicine.The next sections of the work offers models for disease-oriented topics, including cardiac and pulmonary diseases, aging, infectious diseases, obesity, diabetes, neurological diseases, joint diseases, visual disorders, cancer, hypertension, genetic diseases, and diseases of abuse.

• Organized by disease orientation for ease of searchability
• Provides information on locating resources, animal alternatives and animal ethics
• Covers a broad range of animal models used in research for human disease

Part I

Ethics, Resources and Approaches

Chapter 1 Ethics in Biomedical Animal Research

Chapter 2 Access to Resources

Chapter 3 The Advent of the Golden Era of Animal Alternatives

Chapter 4 Environmental Enrichment for Animals Used in Research

Chapter 1

Ethics in Biomedical Animal Research

The Key Role of the Investigator

Jerrold Tannenbaum, School of Veterinary Medicine, University of California at Davis

Outline

Nature and Scope of the Chapter

The Subject Matter of Animal Research Ethics

Aspects of Animal Use and Care Relevant to Animal Research Ethics

Why Investigators are Uniquely Qualified to Engage in Ethical Assessment of Animal Research

The Nature of Principles of Animal Research Ethics

The Need for Scientific Expertise in Applying General Ethical Principles

Why Investigators Should Commit Themselves to Ethical Conduct of Animal Research

Expected by the Law

Necessary for Continuing Public Support

The Right Thing to Do

Why Investigators Play the Key Role in Assuring the Ethical Conduct of Animal Research Projects

The Ethical Significance of Project Goals and Design

General Importance of Project Goals and Design

The Legal Primacy of Project Goals in the US

Constraints on IACUCs and Government Regulators

“Alternatives” and Project Goals

Limited Role of the IACUC

The Key Role of Investigators in Assuring Ethical Conduct of Animal Research

Sources of Support and Guidance in Conducting Ethical Research

Scientific Sources

Ethical and Ethically Relevant Sources

Legally Mandated Ethical Principles

Non-Governmental Documents Adherence to which is Required by Law

Publications of Workshops, Study Committees, and Non-Governmental Entities

Ethical Guidelines of Professional Associations

Developing Useful Ethical Guidelines

Fundamental Principles of Animal Research Ethics

F1. The Biomedical Research Principle

F2. The Animal Research Principle

F3. The Nuremberg Principle

F4. The Pain and Distress Minimization Principle

Ethical Foundations of the Pain and Distress Minimization Principle

Qualifications to the Pain and Distress Minimization Principle

The Incompleteness of the Pain and Distress Minimization Principle

F5. The Pain and Distress Justification Principle

F6. The Harm Justification Principle

Determining the Value of a Research Project

Determining Whether the Value of a Project Justifies any Pain, Distress, or other Harms Caused to the Animals

Reasonable Expectations in Justifying Animal Research Projects

Useful Further Discussion

F7. The Harm Minimization Principle

F8. The General Justification Principle

Applying the General Justification Principle to Projects That Do and Those That Do Not Cause Animals Harm

Why Many Projects That Do Not Harm Animals Are Easily Justified

F9. The Species-Appropriate Housing Principle

Definition of and Ethical Arguments for Research Animal “Well-Being”

Environmental Enrichment

F10. Appropriate Supervision and Care

F11. Research Animals Should Be Treated with Kindness, Compassion, and Gratitude

Practical Ethical Guidelines for Investigators

Some Current Difficult Issues in Animal Research Ethics

The Nature and Ethical Argument for “Alternatives”

The 3Rs as Defined by Russell and Burch

The 3Rs as Tools for Eliminating or Minimizing Animal Pain and Distress

Refinement as Promotion of Animal Well-Being

Replacement and Reduction as Ends in Themselves or Goals Independent of Minimizing Pain and Distress

The Need for Clarity and Argument Regarding the 3Rs

The Nature and Weight of Harms to be Justified by the Value of Animal Research Projects

Unpleasant Experiences Other Than Pain and Distress

Frustration of an Animal’s Nature or Telos

Killing Research Animals

Ethical Relevance of Species and Species Characteristics

The IOM Chimpanzee Report

The Relative Moral Cost View

Criteria for Ranking Species

Number of Ranked Categories

Research Implications of Species Rankings

General Suggestions for Investigators

S1. Communicate to the Public

S2. Become Familiar with the Literature

S3. Participate in Discussions of Ethical Issues Relating to Animal Research

References

Nature and Scope of the Chapter

This chapter presents an overview and explanation of ethical principles that are of crucial importance in the use of animal models for the study of human disease. The chapter is intended primarily for, and is written from the perspective of, scientists who conduct biomedical animal research. Like the other chapters in this volume, the discussion of animal research ethics presented here focuses on matters that are directly relevant to the design and implementation, by investigators, of animal research projects.

Biomedical animal research is founded on an enormously important ethical principle (which is discussed in further detail below): It is among the most noble and indeed imperative of human endeavors to employ scientific research to prevent, alleviate, and cure the pain, suffering, distress, fear, anxiety, disability, infirmity, and death associated with human disease. Because the general decision to use animals to understand human disease is motivated by this high ethical ideal, investigators should want to adhere to the highest ethical standards in the conduct of their research.

After considering the nature of animal research ethics and ethical principles that relate to animal research, the chapter discusses why animal investigators not only are uniquely qualified, but are ethically obligated, to engage in ethical assessment of their work. The chapter presents a number of fundamental principles of animal research ethics, and guidelines for putting these principles into practice. The discussion then highlights several ethical issues regarding which members of the biomedical research community have exhibited some lack of clarity or disagreement. The chapter concludes with recommendations for participation by investigators in ethical discussion of their work, and of biomedical animal research generally.

The chapter does not provide a detailed description of ethical theories that have been applied to animal research by academic philosophers or legal theorists. Nor does the chapter summarize the large (and growing) scholarly literature in animal research ethics. I suggest below that animal researchers become familiar with some of this literature. However, attempting to present comprehensive descriptions of ethical theories or of the animal research ethics literature would preclude this discussion from being useful to investigators. Aside from the fact that many different arguments and conclusions have been offered by different thinkers, much of the animal research ethics literature focuses on a question that has already been answered by scientists who conduct animal research, and by society generally. As stated by one discussion:

At the heart of the wide-ranging and seemingly unending controversy over the use of animals in biomedical science, whether in basic or applied research, toxicity testing, drug production, or education, is one burning question: Are we humans ethically justified in such a use of animals, in general and in particular cases?

Donnelly and Nolan, 1990, p. 8

Clearly, there would be no need for this chapter, and more importantly for animal research ethics, if there were no significant ethical issues relating to the use of animals in biomedical research. However, it is simply a fact that among the most fundamental ethical tenets of contemporary society is not just that we humans are justified in using animals to understand and combat human disease, but that we are often ethically obligated to do so.

The discussion focuses on ethical issues relating to animals kept by research facilities. Experiments and clinical trials conducted by veterinary scientists using privately owned animals (primarily pets) can also play an important role in understanding certain human as well as animal diseases.^2–4 Many of the ethical principles considered in the chapter apply to such research. However, experiments on privately owned animals raise distinctive ethical questions that are not germane to most biomedical animal research, and are therefore not considered here. Such questions include how investigators should obtain informed consent from owners who may be more interested in helping their animals than in contributing to soundly designed experiments, and whether a beloved pet should be kept on an experimental treatment that is not working or is not working as well as a treatment other animals in a study are receiving.⁵

Because animal research is highly regulated by government, the chapter considers ethical standards that are imposed on investigators by law. Also important in ethical assessment of animal experiments are ethical principles that have been adopted by professional organizations composed of scientists, veterinarians, and research animal care specialists. Limitations of space restrict the chapter to discussion of US law, and ethical guidelines of US-based professional associations. It is hoped that readers in other lands will consider how laws and professional guidelines in their countries can inform their judgments regarding ethical conduct of animal research. Indeed, because what is good and right in animal research presumably does not change as one crosses national borders, all investigators may find valuable moral guidance in laws and professional standards of countries other than their own.

As used in the chapter, the term “investigator” refers to principal and coprincipal investigators, but also includes any scientific colleagues who participate significantly in formulating the goals and design of an animal research project. The central theme of the chapter is that investigators—not animal care and use committees, attending veterinarians, or government agencies—play the primary role in assuring the ethical conduct of biomedical animal research.

The Subject Matter of Animal Research Ethics

Numerous ethical questions can be raised that relate in some manner to the use of animals in biomedical research. Some of these questions do not concern whether animal research subjects are treated properly. For example, among the questions that can be asked about the development of animals for organ transplantation to humans are whether certain kinds of animal-to-human xenotransplantation would raise unacceptable risks of infection or disease for transplant recipients, close contacts of recipients, or the general public; and whether because of any such risks, consent to xenotransplants should be exercised not just by recipients but also family members and others.⁶ These questions belong to bioethics and not “animal research ethics” as commonly defined, and as understood in this chapter. Animal research ethics involves issues that pertain to whether animals employed in research are used and treated properly from an ethical standpoint, that is, in ways that accord with human ethical obligations regarding the animals. (Animal research ethics is a branch of bioethics.) There are possible questions relating to xenotransplantation research, for example, that belong to animal research ethics. One can ask, for example, whether some animals used in such research experience significant pain or distress, and if so whether this pain or distress is justified by the value of the knowledge that has been or is likely to be discovered.⁷

Animal research ethics encompasses issues that relate not just to research aimed at understanding human disease, but to other scientific uses of animals, including studies of animal disease; use of animals to test the safety of household products, chemicals used in industrial processes, and cosmetics; and agricultural experiments aimed at producing animals that yield nutritious and palatable food. These uses of animals, and othe...