**2. Trendy outlook**

Animals were used to study human physiology and anatomy in the second century AD as documented by a Greek physician and philosopher, Galen, using mainly apes and pigs [2]. Galen applied his findings directly to humans without considering taxonomic relatedness. It was until the late sixteenth century that this error began to be recognized. Previously in 1865, a French physiologist by name Claude Bernard published the first book, *An Introduction to the Study of Experimental Medicine* [3], advocating the use of chemical and physical induction of disease in animals for biomedical research. Around that same time, Louis Pasteur in France and Robert Koch in Germany introduced the concept of specificity into medicine and the "germ theory of disease."

**Year Nobel Laureate Animal model Contribution to modern medicine**

2013 James E. Rothman Hamsters Discoveries of machinery regulating vesicle traffic, a

2013 Thomas C. Südhof Mice Discoveries of machinery regulating vesicle traffic, a

2012 Sir John B. Gurdon Frogs, mice For the discovery that mature cells can be

2012 Shinya Yamanaka Frogs, mice For the discovery that mature cells can be

2011 Bruce A. Beutler Mice Discoveries concerning the activation of innate

2011 Jules A. Hoffmann Flies Discoveries concerning the activation of innate

2010 Robert G. Edwards Rabbits The development of in vitro fertilization

Monkey, chimpanzee,

mouse

mouse

2008 Luc Montagnier Monkey, chimpanzee,

2011 Ralph M. Steinman Mice For his discovery of the dendritic cell and its role in

2009 Carol W. Greider Protozoan, mouse, frog Discovery of how chromosomes are protected by

2009 Elizabeth H. Blackburn Protozoan, mouse Discovery of how chromosomes are protected by

2009 Jack W. Szostak Protozoan Discovery of how chromosomes are protected by

2008 Harald zur Hausen Hamster, mouse, cow Discovery of human papilloma viruses causing cervical

2007 Mario R. Capecchi Mouse Discoveries of principles for introducing specific gene

2007 Sir Martin J. Evans Mouse, chick Discoveries of principles for introducing specific gene

2007 Oliver Smithies Mouse Discoveries of principles for introducing specific gene

cancer

cells

cells

cells

immunity

immunity

adaptive immunity

Campell and Omura for discoveries concerning a novel therapy against infections caused by roundworm parasites and Youyou Tu for her discoveries concerning

http://dx.doi.org/10.5772/intechopen.70745

5

a novel therapy against malaria

major transport system in our cells

major transport system in our cells

reprogrammed to become pluripotent

reprogrammed to become pluripotent

telomeres and the enzyme telomerase

telomeres and the enzyme telomerase

telomeres and the enzyme telomerase

Discovery of human immunodeficiency virus

Discovery of human immunodeficiency virus

modifications in mice by the use of embryonic stem

modifications in mice by the use of embryonic stem

modifications in mice by the use of embryonic stem

Rats Discoveries of cells that constitute a positioning system in the brain (an inner GPS)

Introductory Chapter: Animal Models for Human Diseases, a Major Contributor to Modern…

Mice, dogs, sheep, cattle, chickens, monkeys

2015 William C. Campbell

Youyou Tu

2014 John O'Keefe and

I. Moser

2008 Françoise

Barré-Sinoussi

and Satoshi Ōmura and

May-Britt and Edvard

It is noted that from 1901, two-thirds of the Nobel Prizes in medicine have relied majorly on animal models for their research, more recently seven (7) of the last ten (10) were animal model-based breakthroughs (**Table 1**) [4]. Researchers now rely heavily on development of animal models to explore all areas of medical science specifically in the assessment of pathogenic mechanisms, diagnostic and therapeutic procedures, vaccine development, nutrition, metabolic diseases, and the efficacy of novel drug development as captured in this book.

A typical instance in the trending use of animals as disease model is the transition from nonhuman primates such as chimpanzee to mouse/rat models in diabetic retinopathy (Chapter 2/3) and in HIV research (chapter 9) [5]. Larger animals are deemed relatively closest to humans (e.g., chimpanzee). However, these animals have become increasingly difficult to maintain and to handle; besides their costly nature. A more disturbing fact is that most human diseases could not be replicated in them, and the causative human agent hardly infects these nonhuman primates as well as difficulty in development of human symptoms and therapeutic responses. Scientists, therefore, resulted to started developing simpler and effective models most especially transgenic (humanized) mouse models [6] that mimic human responses to study and understand various aspects of infectious agents, pathogenesis, disease progression, nature of protective immunity and vaccine development. An ideal animal model for human disease research should possess certain characteristics as a prerequisite for a standard model. The chapters presented in this book elucidate the following notable characteristics of a chosen animal model:



**2. Trendy outlook**

"germ theory of disease."

testing.

Animals were used to study human physiology and anatomy in the second century AD as documented by a Greek physician and philosopher, Galen, using mainly apes and pigs [2]. Galen applied his findings directly to humans without considering taxonomic relatedness. It was until the late sixteenth century that this error began to be recognized. Previously in 1865, a French physiologist by name Claude Bernard published the first book, *An Introduction to the Study of Experimental Medicine* [3], advocating the use of chemical and physical induction of disease in animals for biomedical research. Around that same time, Louis Pasteur in France and Robert Koch in Germany introduced the concept of specificity into medicine and the

4 Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy

It is noted that from 1901, two-thirds of the Nobel Prizes in medicine have relied majorly on animal models for their research, more recently seven (7) of the last ten (10) were animal model-based breakthroughs (**Table 1**) [4]. Researchers now rely heavily on development of animal models to explore all areas of medical science specifically in the assessment of pathogenic mechanisms, diagnostic and therapeutic procedures, vaccine development, nutrition, metabolic diseases, and the efficacy of novel drug development as captured in this book.

A typical instance in the trending use of animals as disease model is the transition from nonhuman primates such as chimpanzee to mouse/rat models in diabetic retinopathy (Chapter 2/3) and in HIV research (chapter 9) [5]. Larger animals are deemed relatively closest to humans (e.g., chimpanzee). However, these animals have become increasingly difficult to maintain and to handle; besides their costly nature. A more disturbing fact is that most human diseases could not be replicated in them, and the causative human agent hardly infects these nonhuman primates as well as difficulty in development of human symptoms and therapeutic responses. Scientists, therefore, resulted to started developing simpler and effective models most especially transgenic (humanized) mouse models [6] that mimic human responses to study and understand various aspects of infectious agents, pathogenesis, disease progression, nature of protective immunity and vaccine development. An ideal animal model for human disease research should possess certain characteristics as a prerequisite for a standard model. The chapters presented in this

**(i)** A close relative or closely associated with the host tissue distribution, disease progres-

**(ii)** Disease course should be relatively shorter in the animal model, to allow for completion of the efficacy test in reasonable time, permitting rapid transition to human clinical

**(iii)** Despite the differences in genetic makeup of humans and animals, there should be suf-

**(iv)** The model should be easy to maintain, work with, easily available in adequate number,

book elucidate the following notable characteristics of a chosen animal model:

sion, and similar route of infection, if not identical.

ficient disease correlation and pathological equivalence.

relatively inexpensive, and free of regulatory constraints.


in the chapters tend to address. Regulatory authorities, however, require vaccine candidates to undergo preclinical evaluation in animal models before they enter the clinical trials in humans [8]. The overarching goal of a new vaccine is to stimulate the immune system to elicit an effective response against the pathogen it is being designed for; currently, experts have noted that no alternatives to the use of live animals exist for evaluation of the vaccine response despite advances in computational sciences for the search of an in silico model. One of the issues bordering scientific expediency in the development and use of animal models is on bioethics and animal rights. Thus, qualification and ethical consideration need appropriate clarification.

Introductory Chapter: Animal Models for Human Diseases, a Major Contributor to Modern…

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7

There is a need to qualify and/or standardize animal models. Qualification of an animal model implies that a specific animal species given a specific challenge agent by a specific route produces a disease process or condition that in multiple important aspects corresponds to the human disease or condition of interest [9]. The experts' discussion (chapters) presents the need for standardization or qualification of models. The question of whether or not there should be a standardized or qualified model is the basis of one of the main current controversies in developing animal models for human diseases. Having a standardized animal model relates to the appropriate research use and may be regarded as a complete and precise description of intended use and application of the qualified animal model in drug development and regulatory processes. The process must specify the details necessary to replicate the

An interesting aspect of the book is the respective discussion in each chapter of next-generation models and how perceived limitations of current animal models could be obviated. Recent animal model research has focused on the (i) refinement of existing models and the development of new ones, (ii) use of these models to research key questions about the disease pathology, and (iii) key findings with these models testing therapeutic and vaccine concepts [10]. Margaret Hamburg wrote "We must bring 21st century approaches to 21st century products and problems" [11]. This scientific era entails rapid and unprecedented development of

**4. Need for standardization of model**

model. Other criteria may be summarized as follows:

**(b)** Known and characterized challenge agent

**(e)** Potential triggers for intervention

**5. Next-generation models**

**(a)** Known and identified animal thus proposed for use

**(c)** Procedural information for the challenge agent exposure

**(d)** Identification of the primary and secondary endpoints

enabling biotechnologies with great promise for the future.

**Table 1.** Contributions of lab animals to biomedical research (adapted from Foundation for Biomedical Research [4]).

#### **3. Expert view vs. common sense**

Many scientific articles and books written in recent times have attempted to bridge the gap between effective animal model and the equivalent human pathological replication. It may seem controvertible on the acceptance of animal models as equivalent to human testing. As this may not apply in all cases, however, there are notifiable instances where animal models may substantially suffix. This is exemplified by the US FDA Animal Efficacy Rule (also known as Animal Rule) which applies to development and testing of drugs and biologicals in animal models to reduce or prevent serious/life-threatening conditions caused by exposure to lethal or permanently disabling toxic agents (chemical, biological, radiological, or nuclear substances) and in instances where human efficacy trials are not feasible or ethical [7].

In this book, animal models of global disease of interest were extensively discussed. The seventeen (17) chapters presented by experienced experts in the field detailed the practical and theoritical steps in animal model development and various approaches to achieve and/or develop specific models X-raying their limitations, interspecies variations, and comparison of different models (chemically induced, biological, xenograft, syngeneic, and genetically modified) which best suited for good experimental results. The book is designed to assist researchers make a beneficial choice of experimental animal relevant to their research design, hypothesis, and expected results. The chapters as much as intriguing presents scientific bases for choice of experimental animals on notable and widely researched global disease of interest ranging from central diabetes insipidus, diabetic retinopathy, hair research and regeneration, skeletal remodeling, ductular reaction in chronic human liver diseases, induced oxidative stress, inflammatory bowel diseases, and double incontinence HIV/AIDS to neuroinflammatory disease.

One of the factors impeding the translation of knowledge from preclinical to clinical studies has been the limitations of in vivo disease models in which specific animal models discussed in the chapters tend to address. Regulatory authorities, however, require vaccine candidates to undergo preclinical evaluation in animal models before they enter the clinical trials in humans [8]. The overarching goal of a new vaccine is to stimulate the immune system to elicit an effective response against the pathogen it is being designed for; currently, experts have noted that no alternatives to the use of live animals exist for evaluation of the vaccine response despite advances in computational sciences for the search of an in silico model. One of the issues bordering scientific expediency in the development and use of animal models is on bioethics and animal rights. Thus, qualification and ethical consideration need appropriate clarification.
