Bacteria become pathogenic under varied circumstances especially when the host defenses become weak due to whatever reasons e.g. poor nutrition. Louis Pasteur, Joseph Lister and others began linking these bacteria to disease and today the discipline of infectious disease has become the greatest ever challenge facing the scientific world. Discovery of Penicillin by Sir Alexander Flemming - its impact and value - was realized as a great breakthrough in the world of life sciences during and after World War II. Advances in medical technology increased our success in combating the bacterial diseases with the manufacture of a variety of antibiotics - tetracycline, streptomycin, ampicillin, amoxicillin etc. and so on - indeed once labelled as the wonder drugs. But today these wonder drugs and their development is no longer an attractive venture for the pharmaceutical companies - why?

Due to ever changing environment - external and/or internal - these bacteria evolved their own mechanism of defense that helps them survive the adversaries of the environment. One theory that shook the entire scientific world and stood the test of the time is the so called 'Theory of natural selection' by Charles Darwin with the core concept that struggle for existence leads to origin of new species and strains. Such species and strains become well equipped to handle the disturbances in their environment including the milieu interior of the human body. During their struggle for existence, these organisms - prokaryotes as well as eukaryotes acquire ever emerging newer mechanisms of resistance that help them overcome the adversaries in environmental conditions by evolving through the process of adaptation - a process of acquiring or developing newer characters which help them survive the adverse environment conditions, and, indeed this 'survival of the fittest', then, leading to emergence of newer species and strains.

By analogy, whenever an antibiotic is administered to eradicate the disease producing pathogenic bacteria, it tends to eliminate not only the pathogenic bacteria but also in the process inflicts damage to the non-pathogenic bacteria, especially 'commensals' that leads to serious disturbances in the milieu interior. At this stage comes struggle for existence for these microbes. Every living being on the planet earth, be it a microbe or human being is, hitherto, provided with defense mechanisms exclusive to the 'one life' itself. This defense arsenal, in microbes exists in the form of resistance mechanisms that lead to microevolution at a fairly rapid rate. Of these, the R-plasmids are the most significant. Exposure of a bacterial population to a specific antibiotic, in the laboratory designed system or within a living system, kills the antibiotic sensitive bacteria but not those that possess R-plasmids or resistance mechanisms. Theory of natural selection predicts that under these circumstances an increasing number of bacteria inherit genes for the antibiotic resistance (microevolution). This resistance, in turn, must spread for the benefit and survival of the entire affected bacterial population to maintain its population dynamics and equilibrium in the given ecosystem.

How the resistance become so common and spreads so fast nullifying effect of the antibiotic is an issue that one needs to delve in. Bacteria, resistant or not resistant, undergo multiplication and proliferation rapidly. For a given E. coli gene, the probability of a mutation averages only about 1x10-7. But since about 2x1010 new E. coli cells are produced daily in the human colon, therefore mutation in each gene will give rise to approximately 2000(2x1010 / 1x10-7) E.coli mutants daily in just one human host. The total number of mutations when all 3000 E.coli genes are considered is about 6x106 (3000x2000) per day. Such new mutations, especially if they carry an antibiotic induced resistance can have appalling impact on genetic diversity - especially because E.coli reproductive rates are very high due to short generation time (20 minutes). Individual bacteria that are now genetically well equipped for the local environment clone themselves more prolifically than do the less fit strains. The resistance spreads (in fact, it needs to spread to survive and evolve) to environment locally, regionally and then globally. To this spread of resistance far and wide across the globe at a very rapid rate, contribute the unique mechanisms of reproduction (which these tiny microbial microscopic lives are naturally endowed with) - such as transformation, transduction and conjugation processes. So, the new species or the strains are now well adapted 'survival of the fittest' and spreads rapidly to restore its own population equilibrium in the vast ecosystem - an ecosystem for these inhabitants of earth that recognize no man made regional demarcations or boundaries. What is the net result?

The antibiotic that triggered all these events now becomes less and less effective, virtually ineffective, undergoing its natural elimination from the market usage culminating into huge economic losses for the pharmaceutical industry, a loss that could run into billions of dollars. The cow gives no more milk - it is dry and dumping this cow (the ineffective antibiotic) needs more investment than the money spent on its manufacture. The problem gets further compounded by the fact that there exist no universally acceptable guidelines to affect the judicious use of antibiotics. The net result is indiscriminate use of these wonder drug - the plethora of antibiotics manufactured all across the globe with the hope that one day at least, it will help, if not eliminate but contain the spread of eradicable bacterial diseases.

Lifetime drugs that humans use, of and on, for entire lifetime, for example paracetamol - in striking contrast - do not act against any life form. Such drugs interact with the cell(s) at a molecular level and bring about temporary changes in the functioning of the host cell which returns to normal when the effect of the drug is over or the drug is withdrawn. The cell damage even if it occurs - undergoes natural repair and physiological restoration leading to the return of the cells, the organ and the system to its normal structural and functional status - physiologically as well as anatomically. Lifetime drugs continue to be of use throughout life of an individual without inviting any resistance to its occasional or repeated use and effects. In fact, for a pharmaceutical company improvement in the design of the lifetime drugs is more fruitful - a new fancy preparation in the market under a new trade name. Therefore, manufacturing of life time drugs is like breeding and cloning cows that continues to give milk for ever - a functional asset with good marketable values for long times ahead when compared to antibiotic manufacturing whose future always remains in dole drums, not only because of the resistance phenomenon but also because of its indiscriminate use.

Dr Balvinder Arora is pursuing CRA program from Kriger Research Center, Toronto, Canada and Dr Sandeep Bagga is a Certified Bioinformatics Specialist, Cert. in SAS Programming and associated with Pharmaceutical Research and Clinical Trials, PRACT Advisory Service, Sterling, Virginia (USA).