**4. Need for standardization of model**

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 model. Other criteria may be summarized as follows:


### **5. Next-generation models**

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

2004 Richard Axel Mouse, *Drosophila* (fruit

2003 Paul C. Lauterbur Clam, mouse, dog, rat,

flies)

frog

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

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

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

chimpanzee, pig, rabbit,

2006 Andrew Z. Fire Nematode roundworm Discovery of RNA interference—gene silencing by

2006 Craig C. Mello Nematode roundworm Discovery of RNA interference—gene silencing by

2005 Barry J. Marshall Piglet Discovery of the bacterium *Helicobacter pylori* and its

2004 Linda B. Buck Mouse Discoveries of odorant receptors and the organization

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

(MRI)

double-stranded RNA

double-stranded RNA

of the olfactory system

of the olfactory system"

role in gastritis and peptic ulcer disease

Discoveries of odorant receptors and the organization

Discoveries concerning magnetic resonance imaging

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 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 enabling biotechnologies with great promise for the future.

#### **6. What this book argues**

As implied above, the concept of animal models dealt with in this book discusses appropriate mechanistic models for selected prevalent human diseases. An animal model is imperative for preclinical trials, disease pathway and pathological elucidation, new drug development, and vaccine construction. Against any odd, the use of animals especially rat and mouse seems indispensable in today's scientific world. The book presents reproducible experimental approach using animal models for human diseases with measurable equivalence to that of humans. It also presents models of high human predictive value. Despite the current insights and promising technologies, no scientific method can at this time fully address the limitation(s) of using animal models as complete surrogates for humans.

[8] Gerdts V, Wilson HL, Meurens F, van Drunen L, van den Hurk S, Wilson D, Walker S, et al. Large animal models for vaccine development and testing. ILAR Journal. Oxford

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

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

9

[9] Product Development Under the Animal Rule Guidance for Industry. U.S.Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). https://www.fda.gov/downloads/drugs/guidances/ucm399217.pdf October

[10] Hessell AJ, Haigwood NL. Animal models in HIV-1 protection and therapy. Current

Opinion in HIV and AIDS. NIH Public Access. 2015;**10**:170

[11] Hamburg MA. Advancing regulatory science. Science. 2011;**331**(6020):987

University Press. 2015;**56**:53-62

2015 Accessed: 12 June 2017

#### **Author details**

Ibeh Bartholomew Okechukwu

Address all correspondence to: barthokeyibeh@yahoo.com

Laboratory of Animal Models for Human Diseases (LAMHD), Medical Biotechnology Department, National Biotechnology Development Agency, Abuja, Nigeria

#### **References**


**6. What this book argues**

**Author details**

**References**

Ibeh Bartholomew Okechukwu

As implied above, the concept of animal models dealt with in this book discusses appropriate mechanistic models for selected prevalent human diseases. An animal model is imperative for preclinical trials, disease pathway and pathological elucidation, new drug development, and vaccine construction. Against any odd, the use of animals especially rat and mouse seems indispensable in today's scientific world. The book presents reproducible experimental approach using animal models for human diseases with measurable equivalence to that of humans. It also presents models of high human predictive value. Despite the current insights and promising technologies, no scientific method can at this time fully address the

Laboratory of Animal Models for Human Diseases (LAMHD), Medical Biotechnology

[1] Rand MS. Selection of Biomedical Animal Models. In: Conn PM, editor. Source Book of Models of Biomedical Research. Totowas, NJ: Humana Press Inc.; 2008. p. 9-15

[2] Charles Singer Galen as a modern. Section of the history of medicine. Proceedings of the

[3] Bernard C. An Introduction to the Study of Experimental Medicine. 1st ed. USA: Henry

[4] Foundation for Biomedical Research. Animal Testing and Nobel Prize. https://fbresearch.

[5] Haigwood NL. Update on animal models for HIV research. European Journal of

[6] Bartholomew I, Yasuhide F, Lucy O, Josiah H. Humanized mouse as an appropriate model for accelerated global HIV research and vaccine development: Current trend.

[7] Snoy PJ. Establishing efficacy of human products using animals: The US food and drug

Schuman Inc.; 1865 Transl. Henry Co–pley Greene, AM. 1929. p. 4-250

org/medical-advances/nobel-prizes [Accessed: 14th May, 2017]

Immunopharmacology and Immunotoxicology. 2016;**38**(6):395-407

administration's 'animal rule'. Veterinary Pathology. 2010;**47**(5):774-778

limitation(s) of using animal models as complete surrogates for humans.

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

Department, National Biotechnology Development Agency, Abuja, Nigeria

Address all correspondence to: barthokeyibeh@yahoo.com

Royal Society of Medicine. 1949;**XLII**:563-570

Immunology. 2009;**39**:1994-1999

**Section 2**

**Diabetics and Obesity**

**Diabetics and Obesity**

**Chapter 2**

**Provisional chapter**

**Animal Models of Diabetic Retinopathy (Part 1)**

**Animal Models of Diabetic Retinopathy (Part 1)**

DOI: 10.5772/intechopen.70238

Diabetic retinopathy (DR) is one of the leading causes of preventable vision impairment and blindness in the working-age population worldwide. Numerous animal models have been developed for therapeutic drug screening and to further our understanding of the molecular and cellular pathological processes involved in DR. In this book chapter, we describe the cellular, molecular and morphological features of mouse models of DR as well as their respective advantages and limitations. To date, no animal model can holistically reproduce the pathological progression of human DR; most only display early or advanced lesions of DR. However, a thorough understanding of genotypic and phenotypic expressions of existing models will facilitate researchers' selection of the appropri-

**Keywords:** animals, blood glucose, blindness, diabetic complications, diabetes mellitus/

Diabetes mellitus is a growing epidemic and a major contributor to the global burden of disease [1]. Insulin deficiency leading to hyperglycemia occurs in type 1 diabetes (T1D or insulindependent diabetes mellitus) as a result of autoimmune destruction of pancreatic beta islet cells. Type 2 diabetes (T2D or non-insulin-dependent diabetes mellitus) is characterized by insulin resistance, often due to physical inactivity and obesity, and may progress to impaired insulin production. T1D is unpreventable as of current understanding, while T2D, the more

pathology/physiopathology, neovascularization, proliferative, retinal vessels

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and one of the leading causes of preventable vision impairment and blindness in the

Larissa H.C. Tang, Ian Y.H. Wong and Amy C.Y. Lo

ate model to simulate their desired clinical scenarios.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70238

Larissa H.C. Tang, Ian Y.H. Wong and

Amy C.Y. Lo

**Abstract**

**1. Introduction**

common type of the two, is preventable.

**Provisional chapter**
