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Antibiotics: A biography

Today, less than 100 years after the serendipitous discovery of penicillin, antibiotics have almost become a household remedy. Though we were quick to exploit the therapeutic values of antibiotics, for too long we paid scant heed to the sustainability of these wonder drugs (long-term thinking has rarely been mankind’s forte). 

In a few decades, antibiotics may very well be as useless as placebo sugar pills. On the bright side, a few of us at least are watchful of fast-approaching threats. For years now, scientists have issued dire warnings about the dangers of antibiotic resistance (unfortunately, we still have a long way to go). But before we get into why that is, let’s consider a simple question: exactly what are antibiotics? 

It may surprise you to know that antibiotics were not made by, or for, humans. Many microbes produce various substances, including antibiotics, to kill other microbes that are their competitors for food and space. Humans just happened to find a way to take advantage of this microbe-on-microbe conflict. 

The molecular weapons deployed are nasty chemicals which can harm the enemy in different ways. They can bore holes in the sheath that protects microbial cells. Or they can short circuit important life processes when ingested. 

The microbial artillery of antibiotics varies widely, with different capacities and specificities. Some antibiotics merely arrest the growth of their enemy, while others outright kill their target. Every environment on the planet—from soil to water to sand to the bodies of other living beings (like us)—is the battleground for this bacterial warfare for food and space. 

Some of the parties involved bode ill for human beings. Our organs are 'space' for them, and the stuff inside those organs, including our cells, serves as food. Our natural defences against these enemies: the wonderfully complex and effective human immune system. 

The battle has been raging for millions of years—our ancestors, and the ancestors of the microbes we battle today, kept evolving new weapons and defence systems. Each side loses some of its battles and, quite naturally, in spite of multiple lines of defence employed by our immune system, bacterial infections can often maim or kill. This happens most often when the immune system is not at its best—for instance, when an individual is severely wounded or suffers from long-term illnesses, or when people are on immunosuppressive medication. 

Wonder drug

The discovery of antibiotics was a fortunate accident. On 3 September 1928, in St Mary’s Hospital in London, Alexander Fleming, a professor of bacteriology, found something curious while studying a Staphylococcus specimen (this particularly notorious bacterium is often responsible for food poisoning, abscesses, boils and sore throats). 

Fleming saw that the petri dish was full of Staphylococcus colonies, thriving on the nutritious jelly, save for a blob of unwanted fungus growing in the middle and a nice clear zone around it. Clearly, the fungus was somehow inhibiting the growth of Staphylococcus. A substance oozing out of the miracle fungus was later identified as penicillin. The rest is history. 

Let’s come back to the present for now. We have reached a stage where antibiotics have become an indispensable part of our medical system. Hundreds of different antibiotics have now been identified and many more are discovered every year. Their chemical structure, mechanism of action and possible targets are well known. 

Scientists first found the microbes that make the weapons against microbes that infect humans, and then devised a way to separate these weapons from their makers. Afterwards, they took it a step further and synthesized antibiotics chemically, without any microbial aid. 

In 2000, a staggering 150 million pounds (68 million kg) of natural and synthetic antibiotics were produced worldwide. We use antibiotics not only to treat the bacterial infections but also to prevent infections.  

So, what's the problem?

Amid all this, though, we underestimated the bacteria. Not unlike us, microbes have millions of years of experience in this warfare and over time, more and more grew resistant to the antibiotics. Our estimates for the evolution and spread of these defence strategies, unfortunately, were quite off the mark. 

In 1950, 20 years after penicillin was discovered, scientists were largely of the opinion that antibiotic resistance would be a rare phenomenon. We now have ample evidence to the contrary. 

In the face of the antibiotic menace, microbes evolve different kinds of mechanisms to render the drugs useless. For instance, one common strategy is to recognize the harmful antibiotic and pump it out of the cell. Another is to change the structure of the the socket where the antibiotic would plug in, preventing the short-circuit. A microbe with any of these tricks, unhindered by the presence of antibiotics, will reproduce happily.

And what’s more, once evolved, the genes for resistance are swiftly circulated through a microbial game of passing the parcel. Unfortunately, the music never stops and the resistance can spread across continents. On top of that, it is only (relatively) recently that we began to fathom the magnitude of this problem. And when it comes to predicting the course of antibiotic resistance, we are only slightly better than cavemen trying to judge the distance between the moon and the earth. 

The laws of physics allow us to predict the movements of planets and stars. Remember that scene from 2001: A Space Odyssey (the book, not the film) where a spaceship uses the gravitational field of Jupiter to speed itself up, sort of like a slingshot, and propels itself towards Saturn? Well, we’ve actually managed to pull off something similar, during the Voyager launch. And with superb precision. The same, alas, cannot be said for most of things in biology. 

The most important reason for this failure is the fact that, unlike astrophysicists, biologists deal with living things. In the antibiotic wars, we fight against beings that have been selected through billions of years of evolution and whose survival skills are second to none. 

A way out

Does this mean that the trick, i.e. resistance to any given antibiotic, needs to evolve only once on our planet? Before spreading to every microbe? 

Not at all. Life is rarely wasteful—if there isn’t an antibiotic in the environment of the microbe, building the defences to keep it out is a waste of energy. If the antibiotic is not encountered for a long time, storing and sharing the defensive trick is also a waste. 

And there lies the crux of the problem. We now use antibiotics to such an extent that most environments are teeming with them. The pressure to retain survival techniques is always on. And hence the resistance is persisting and spreading. 

What does this mean for us? Soon, antibiotics might not be effective at thwarting the infections. We might have to suffer our day-to-day infections a bit longer. But we still have our almighty immune systems, right? 

Yes, we do. But many medical procedures, from common surgeries to cancer treatments to organ transplants, involve the active suppression of immunity. The patient faces a tremendous risk of infections. Simple accidents, like stepping on a nail, could prove tragic in the absence of effective antibiotic treatment. 

This might sound overly pessimism to many, but unless we take immediate measures, it may become reality in the not-too-distant future. 

This brings us to another question: what is it that we can do? Currently, our best bet is the moderation of antibiotic use. How, though, can we achieve this without serious drawbacks? There are quite a few options. 

One is to minimize the administration of antibiotics to domesticated animals. Nearly 50% of antibiotics produced in the world are administered to animals, not as a treatment, but to improve the yields of meat. 

Two, for humans, antibiotics are often prescribed before the disease-causing agent is identified. In the majority of instances, the culprit is some kind of virus, against which antibiotics are useless. But testing samples of bodily fluids is costly and time consuming. This results in blind prescription of antibiotics—sometimes even a cocktail of them—by physicians. 

In many countries, India included, antibiotics can be bought over the counter without a prescription, and hence are consumed more than actually necessary or even effective. 

If globalization has bought world the closer, it has also bought its own “global” problems with it. We should try, and I dare say we are trying, to fight them globally. 

Across the world, attempts are being made to regulate the usage of antibiotics. Scientists are trying to discover more and better antibiotics, as well as new ways to utilize the existing repertoire. We might even stumble upon a new wonder weapon. But these attempts will require much time and, of course, large amounts of money. For now, though, we must build awareness of the issue and minimize the use of antibiotics. 

Shraddha Karve is postdoctoral scientist at University of Zurich. 

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