Applications for Drug Development

Authored by: Jessica Kalra , Donald T. Yapp , Murray Webb , Marcel B. Bally

Handbook of Small Animal Imaging

Print publication date:  April  2016
Online publication date:  February  2016

Print ISBN: 9781466555686
eBook ISBN: 9781466555693
Adobe ISBN:

10.1201/b19052-35

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Abstract

For a large part of human history, drugs derived from plants, animals, and minerals were discovered through experimentation and observation in both humans and animals. Scientists such as Edward Jenner (1749–1823) were even able to test some of their ideas in humans. For example, Jenner’s observation that milkmaids showed immunity to small pox led to his hypothesis that the fluid from a woman with a cow pox blister may provide protection to others. In order to validate this theory, Jenner inoculated the suppurate material into a young boy and challenged the subject with two rounds of small pox (Willis 1997; Tan 2004). By doing this, Jenner demonstrated the concept of passive immunity, and laid the foundations for contemporary immunology. It was not until the 1800s, when human testing came under great scrutiny, that a larger emphasis was placed on tests in animal models. Starting with the discovery of diphtheria toxin and antitoxin in the late 1880s (Holmes 2000), animal models have become standard in the scientific assessment of new chemical agents and a means through which scientists can gain a broader understanding of complex disease processes. One of the most significant examples of the utility of animal models in drug discovery was by the renowned scientist Louis Pasteur (1822–1895). His study of infectious disease in animal models led to the development of vaccines against both cholera (Smith 2012) and rabies (Horsley 1889; Smith 2012). As discussed by Devita et al. in a detailed review on the history of cancer chemotherapy, Paul Ehrlich (1854–1915), the German physician and scientist who coined the term “chemotherapy,” was the first to use animals to screen a small number of chemicals for activity against disease (DeVita and Chu 2008). In 1921, Dr. Frederick Banting and Dr. Charles Best established the first animal model of diabetes by removing the pancreas from previously non-diabetic dogs. More importantly, by grinding up excised pancreatic tissue and extracting specific substances, the researchers identified the hormone insulin and demonstrated that the injection of purified insulin in diabetic dogs was able to control blood sugar levels (Banting and Best 1990; Rafuse 1996). George Clowes (1877–1958) of the Roswell Park Memorial Institute (RPMI) established the first transplantable tumor systems in rodents (DeVita and Chu 2008), which led to the testing of a large number of chemicals for antitumor activity (DeVita and Chu 2008). From the early 1900s onwards, research efforts have focused on identifying the ideal animal model for drug testing, an effort that continues to this day.

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