HISTORICAL DEVELOPMENT OF ANTIBIOTICS

1. HISTORICAL DEVELOPMENT OF ANTIBIOTICS

Paul Vuilemin (1889) was the first and foremost scientist who vehemently promulgated the very concept of ‘antibiotic’ activity to introduce the terminology ‘influences antibiotiques’ (or antibiotic influences ) in order to describe the prevailing negative interactions amongst the animals and plants.* Later on, Walksman (1940s) eventually coined the term ‘antibiotic’ and also introduced a plausible definition as — ‘a chemical substance derived from microorganisms which has the capacity of inhibit- ing growth, and even destroying, other microorganisms in dilute solutions’.**

Another school of thought advocates that the natural product antibiotics essentially comprise of a specific category of chemical entities invariably termed as the secondary metabolites. Besides, on

a rather broader perspective such substances may be characterized for possessing chemical structures which are found to be quite unusual when compared with those of the intermediary metabolites. Nev- ertheless, such natural product antibiotics, are being generated at an extremely low ebb specific growth rates, and also supported by the fact that these are not absolutely essential the growth of the ‘producing organisms’ in a pure culture medium. In fact, the ‘antibiotics’ are observed to be of highly critical nature with respect to the producing organisms in their usual natural environment because their pres- ence is an absolute must not only for the survival but also for the competitive advantage.***

However, the most widely accepted definition of an ‘antibiotic’ promulgated by the scientific jargons is — ‘a chemical substance produced by a microorgansims, that has the capacity, in low con- centration, to inhibit or kill, selectively, other microorganisms’.

Importantly, the aforesaid definition**** lays particular emphasis on the terminologies like ‘se- lectively’ or ‘selective toxicity’ that explicitely suggests that the substance either checks the growth of

* Levy SB : The Antibiotic Paradox : How Miracle Drugs Are Destroying the Miracle, Plenium Press, New York, 1992.

** Vandamine EJ, Antibiotic Search and Production : An Overview, Vandamine EJ (ed.) Biotechnology of Antibiotics, Marcel Dekker, New York, pp. 3–31, 1984.

*** Demain AI : Functions of Secondary Metabolites : Hershberger CL et al. (eds.) Genetic and Molecular Biology of Industrial Microorganisms, American Society for Microbiology, Washington DC, pp. 1–11, 1989.

**** Kar, A : Pharmacognosy and Pharmacobiotechnology, New Age International (P) LTD., Publishers, New Delhi, pp. 654–800, 2003.

PHARMACEUTICAL BIOTECHNOLOGY

pathogens or exerts a bactericidal action on the microbes without displaying a similar action on the host organisms i.e., the humans.

Interestingly, one may evidently observe from the above cited definition(s) that critically ex- cludes the plethora of never medicinal compounds essentially having the pure synthetic genesis (origin). In reality and actual practice, these ‘synthetic substances’ are virtually treated at par with the host of

natural compounds together with their respective derivatives under the terminology ‘antimicrobials’ that could be further sub-divided predominantly into two categories namely : antifungals and antibacterials depending on the specific type(s) of microbe undergoing inhibition. Therefore, in order to circumvent the practical aspects, both the terminologies, viz., ‘antibiotic’ and ‘antimicrobial’ may

be used effectively and interchangeably irrespective of the specific source of the chemical entity.

In general, the ‘antibiotics’ are produced on a large scale by three well-known and defined methodologies, such as : (a) fermentation process ; (b) semi-synthetic process ; and (c) synthetic process. A tremendous quantum leap and qualified successful diversification in the specific field of ‘biotechnology’ has helped the first two processes (i.e., ‘a’ and ‘b’) in accomplishing an enormous enhancement in the rate of production as well as improved upon their yield and purity.

Antibiotic Development : The latest progressive trend in the logistic aspects of antibiotic de-

velopment may be observed vividly by the under mentioned sequence of goals and objectives, such as : • To screen and evaluate different types of sources of microorganisms for the detection of

purposeful antagonism.

• To identify and select modified versions of microbial mutants, establish optimal environ- mental and nutritional conditions, and to develop suitable technique(s) for the recovery of

antibiotics from cultures,

• To induce the production of particular desired metabolites, • To improve upon and modify the fermeutative metabolites either by the aid of biological and

chemical manipulations to accomplish more useful antibiotic substances, • To develop an elaborated methods for the ‘total synthesis’ of antibiotics from ab initio for a

feasible economic advantage, and • To make use of an ‘adjunct agent’ to distinctly enhance the impact or availability of an

antibiotic.