Here is a short excerpt from Chapter 14.
“The proper study of Mankind is Man.”
—Alexander Pope in “An Essay on Man,” 1734.
Common diseases are complex, as is the response of humans to treatments for the common diseases. Are we likely to find adequate animal models for common diseases?
14.3.1 Rule—For the common diseases of humans, there are no adequate animal models.Rodents, especially mice and rats, are often used in disease research. Historically, the drug development process employs mouse models to identify candidate drugs for clinical trials in humans . Few such mouse-inspired trials have shown success [21–24]. In a review of human clinical trials based on research data collected from mouse models, every one of 150 clinical trials of inflammatory responses in humans was a failure . In the vascular field, there are animal models for stroke. Based on animal models, about 500 candidate drugs were proposed as neuroprotective agents in human stroke. Of the 500 candidate drugs, only two were shown to be of value for humans .
Brief Rationale—The common diseases are complex, the end result of many genetic and environmental factors. There is no reason to expect that a complex set of factors interacting in humans could be replicated in an animal.
In the field of cancer research, carcinogens induce cancers in rodents, and the cancers that occur in rodents and humans share a set of fundamental properties: continuous growth, autonomous growth, invasiveness, metastasis (see Glossary item, Autonomous growth). Beyond these features, most animals models deviate from their human counterparts. Here just are a few examples:
- Rodent tumors develop over a very short period of time, limited by the short life expectancy of the mouse or rat. A strong carcinogen can produce palpable mouse tumors in mere weeks. The commonly occurring tumors in humans require years to develop.
- In most strains of rodent, tumors lack molecular markers commonly found in human tumors (e.g., p53). The cytogenetic markers for rodent tumors are different from the cytogenetic markers for human tumors. In fact, the karyotype, physical mappings of genes, causal genes, and gene polymorphisms of rodent tumors are all quite different from human tumors (see Glossary items, Synteny, Haplotype).
- Animals metabolize drugs differently compared to humans.
- Viruses, bacteria, and other organisms that cause human cancer are different from the organisms causing cancer in animals.
- The diet of animals is different from the diet of humans.
- The host factors of animals, including immune status, are different from those of humans.
I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.
- Jules J. Berman, Ph.D., M.D.
tags: rare disease, animal models, carcinogenicity, cancer models, tumor models, drug development, drug trials, new drugs under development, rare disease research, rare diseases, orphan diseases, orphan drugs