The Rise of the Resistance: How Antibiotics Work
In 1928, Alexander Fleming discovered penicillin, the first antibiotic discovered by mankind. He would eventually go on to win the Nobel Prize for this achievement, a well-deserved honor undoubtedly. The discovery itself is a bit of a humorous story, one of those moments in science that manifested as less of a “Eureka!” and more of “Hmmm, that’s interesting…” Regardless, the discovery would ultimately revolutionize the medical field and help usher us into the modern age of medicine.
Although science history is fun to know, this post is not about where we’ve been; it’s about where we are now. We are in the twilight years of the Age of Antibiotics and it’s important to understand what that means for medicine and the world. But in order to understand how we got to this point, we first have to understand what antibiotics actually are, how they work, and how resistance has developed.
So what are antibiotics? As most people know them, antibiotics are medicines that are used to treat infections. However, it’s a little more complicated than that. See, infections are caused by microbes or microorganisms, which is just a fancy science way to say really, small living things. That being said, these microbes can be bacteria, viruses, fungi, and a handful of other things.
Each one of these things is distinctly different from the others and although I won’t get into the specifics here, what you need to know is this: antibiotics are used for treating bacterial infections. Side note: there are actually some valid exceptions to that, but let’s just keep things “textbook” for now. So, that being said, if you have the flu (a viral infection), antibiotics won’t do anything to help you.
So where do we get these things anyway? Most people believe that antibiotics are these miracle drugs that scientists just cook up in a lab. Although we mass produce them in labs now, microbes actually make antibiotics themselves (bacterial and fungal species). An important thing to understand is that there are many different species of bacteria and not all of them are friends. They can be selfish and are very interested in self-preservation; that is, they don’t play nice when it comes to protecting themselves. Because of this, bacteria can engage in “turf wars,” essentially saying, “This is my area, so keep out!” So in order to “fight”, they produce these compounds to selectively kill the other bacteria. We call these compounds antibiotics.
That brings us to our first main point: antibiotics are selective, meaning that certain antibiotics can only kill certain bacteria. To date, there is no antibiotic that can effectively kill all bacteria. And if you think about it, it makes sense. Bacteria make these things to kill other bacteria. What good would it do the bacteria to make something that kills itself as well?
So then about resistance: what is it? Well, without getting in the nitty gritty biology and genetics behind it, resistance is simply when a given bacterium becomes “immune” to a given antibiotic. That is, a certain antibiotic that should kill the bacteria no longer works. This can happen in a variety of ways, but really it’s just basic evolution. This is our second main point: Bacteria can evolve. Nothing in nature stays the same forever. And if you keep trying to kill the bacteria with antibiotics, then the only ones you have left (the survivors) are the resistant ones.
It’s important to understand this concept, so let’s take a moment to really spell it out. First we need to acknowledge that diversity naturally exists in life. Even within a single species of bacteria, diversity exists among them. They are not exact clones of each other and so they have different traits, similar to how you and your siblings are related, but aren’t exactly the same. And in a happy and safe system, with no threats at all, these differences are simply just differences. Not advantages or disadvantages. Just different.
But when you expose bacteria to antibiotics, now there is a threat. So suddenly these differences aren’t nothing factors anymore. Those little, seemingly insignificant, differences before can suddenly become a strength or a weakness. Antibiotics work by targeting really specific features of a bacteria, exploiting certain weaknesses or disabling certain functions they need to survive. In humans, this would be the equivalent of stabbing someone in the heart or suffocating them. This is what antibiotics essentially do to bacteria. But what if there was a human that was different in some way, such that it didn’t need its heart to live? Or if it didn’t need to breathe air? What if it had randomly developed these changes by chance? That human would be resistant and survive. It’s the same for bacteria. With no threats to the bacteria, these differences don’t really matter. But when exposed to an antibiotic, these differences can literally determine whether the bacteria live or die.
Let’s see an example of this in action: In a single species of bacteria, we have a coloring-trait that makes the bacteria: green-colored, blue-colored, or red-colored; it’s the same species of bacteria, just with different traits. With no threats, these bacteria will just continue to exist with this diversity. But if we expose them to an anti-red antibiotic, they only left will be the green and blue colored ones. In application, if someone happens to be infected with the green or blue bacteria, the anti-red antibiotic will no longer work. And thus, this bacteria is now resistant to anti-red.
We can illustrate this even further, with the same thought experiment, except this time with blue, cyan, and purple colored bacteria. We can treat with an anti-blue antibiotic and let’s assume that cyan is close enough to blue that the anti-blue kills it too. But purple is different enough and survives. You can see from this, that after some time has passed, the bacteria have grown back and now they’re all purple. You can treat with anti-blue again, but it’s not going to work. These bacteria are now resistant. This is particularly significant when you compare it to the original sample. The purple were definitely in the minority at the start (when there were no threats to the bacteria). The purple trait didn’t matter then; they were just different. But in the end, after the antibiotic treatment, they completely dominate. This is how antibiotic resistance develops.
These illustrations may seem simple and light-hearted, but this threat is very real. And unfortunately, it’s not an exaggeration to say it’s a matter of life and death. The bacteria we treat with antibiotics stand a good chance of killing us if left untreated. Infection has been one of humanity’s greatest threats since the dawn of our species and it’s only recently that antibiotics have given us an edge.
In a natural, non-medical, environment, bacteria and other microbes constantly make antibiotics to combat one another, in a sort of microbial warfare. And, as with actual warfare, when someone makes a newer and better weapon, you need to find new ways to defend yourself. It’s either that or go extinct. So the development of antibiotic resistance is a natural occurrence. Bacteria and microbes have always existed in this perpetual arms race with one other, a continual tug-of-war that ultimately always finds itself pulled back to the middle.
However, with the advent of human medicine, we’ve shifted this arms race against the bacteria. We’ve produced antibiotics in massive, unprecedented numbers and relentlessly used them to treat infections. For those infectious bacteria, their choices were simple: go extinct or up the ante. They chose the latter. By treating infections with antibiotics, we’ve forced them to evolve faster. And so, in this way, human medicine has propagated the rise of antibiotic resistance. Antibiotic resistance is a natural, normally occurring phenomenon. But the problem is now it’s happening faster than ever and we’re no longer sure we can keep up.