Federation of American Scientists Case Studies in Dual Use Biological Research Module 5.0: Antibiotic Resistance Case Study
Topic: History of Antibiotics

Antibiotics are a broad class of chemicals that are capable of either inhibiting growth or killing bacteria. They interfere with metabolic processes necessary for bacteria to grow, but do not typically harm human cells. There are several different classes of antibiotics with a variety of molecular targets. For example, both penicillin and vancomycin, obstruct cell wall synthesis in gram-positive bacteria causing them to lyse. Because they only affect gram-positive bacteria, penicillin and vancomycin are considered “narrow spectrum” antibiotics. Tetracyclines, on the other hand, are “broad-spectrum” antibiotics that act on both gram-positive and gram-negative bacteria to impede protein production by binding to ribosomes and reducing their activity.

Following the discovery of penicillin from Penicillium mold, researchers were able to identify and isolate new antibiotics from soil bacteria and fungi. An article in the New England Journal of Medicine reported that between 1940 and 1970, ten entirely different classes of antibiotics, each with unique targets or modes of action were identified. However, from 1970 until the late 1990’s all new antibiotics were derivatives of these existing classes. For example, based on the chemical structure of penicillin, several synthetic variants have been produced that keep the pharmacologically active part of the chemical, but circumvent resistance by modifying other parts of the structure. Ampicillin and amoxicillin are penicillin-variants developed in this manner which also turned out to be broad-spectrum antibiotics.

A 2006 study in Nature Biotechnology found that since 1998 only four antibiotics exhibiting a new mechanism or significantly different chemical structure have been approved by the US Food and Drug Administration (FDA). They also found that only six antibiotics were in phase 2 or phase 3 clinical trials as compared to 313 other drugs, and that only eight of fourteen major pharmaceutical companies they surveyed appeared to be conducting antibiotic research and development.


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