Antibiotic Resistance and Evolution

Understanding What Really Happens

Today, I want to talk about bugs, little tiny, microscopic bugs – the ones that we commonly call bacteria. Okay – technically speaking they aren't bugs, but they sure can annoy us like bugs if they are the unfriendly type. You know the kinds I'm talking about – tuberculosis, cholera, e.coli and more. These bugs (er, bacteria) are unwanted guests, and we generally great them with one of modern mans greatest friends – antibiotics.

Ah, antibiotics – the promise, the hope, the dreams – a life free of the worries of those nasty little disease causing bacteria. But alas, the dream, while still alive, isn't quite as pleasant as we imagined it would be. It seems that those pesky little intruders have a few tricks up their sleeves and are able to resist antibiotics.

And that is where are story begins.

You see, the question is not do bacteria become antibiotic resistant, but how do they become antibiotic resistant and what does this indicate in terms of the theory of evolution? Antibiotic resistance is used as evidence for a great evolutionary process, one starting from the first cells up to you and I today.

So let's see how good the evidence is – what can we learn from antibiotic resistance in terms of evolutionary theory and what can we not learn. Please note – I am not discussion the theory of evolution as a whole or whether or not anything like evolution happened. My focus is much simpler, what can we logically and reasonably learn from antibiotic resistance to the theory of evolution.

So with that said, let's see what these little bugs (oops, there's that word again) have to teach us.

The Standard Story

Let's start with the standard line about antibiotic resistance.

It goes something like this – some bacteria, vis-a-vis random mutations that happen when copying a bacteria's DNA, provide the bacteria with resistance to antibiotics. This resistance allows them to reproduce, whereas the other bacteria get killed off by the antibiotics.

The resistant bacteria is thus able to dominate and take over the general bacterial population and thus evolve into a new, stronger, more adaptable strain of the original bacteria. Thus random mutations plus natural selection have led to an improved bacteria.

That, I believe, is a fair representation of the most common explanation, and it is illustrated in a rather entertaining manner by this video:

A More Accurate Understanding

Okay, not that we've got the standard line covered – let's learn what really happens in the real world. My main source material will come from a nine-minute animated film by the FDA called The Animation of Antimicrobial Resistance. This film will probably not become a block-buster hit, but it does make it very easy to understand some otherwise difficult to understand concepts in biology.

Please note – it is essential to watch this film to intelligently discuss this issue (for those of you who prefer text, you can find a transcript here). So take a moment and see what it has to say and then see my thoughts and comments below:

Expected Phenomenon

Note the claim that the mechanisms discussed in this film are "expected phenomenon of the Darwinian biological principle of 'survival of the fittest'". Let's refresh our understanding of this principle.

Those organisms with a survival advantage will survive, those without that advantage will not. If two people are shot in the chest and one is wearing a bullet proof vest and the other one isn't, then more likely than not the one wearing the bullet proof vest will survive, the one without the vest will not. That seems obvious and true.

But the real question here is how do these bacteria get the equivalent of a antibiotic proof vest? Where do these 'vests' come from? How do they develop? And, most importantly, how do they spread to the rest of the population. Merely stating that the fittest survive doesn't really tell us anything, it's a truism. What we need to know is how does one member of the group become the fittest and how does he pass that fitness on to other members of the group.

A Little Break for Something Fishy

I do have to say that there is something strange about this statement about the Darwinian biological principle and expectations. Take a listen to the following sentence and tell me whether or not you think it seems to be a later addition added into the film:

The increased prevalence and dissemination of resistance is an outcome of natural selection and should be viewed as an expected phenomenon of the Darwinian biological principle of "survival of the fittest."

I've listened to this line a few times and the voice over for this one line seems to be a different person than the voice-over for the rest of the film. I think this is significant because the mechanisms discussed in this film (except for mutations) actually do not support the standard Darwinian principle and are not at all expected or predicted by it.

It's almost as if someone in the FDA does not want us to draw the right idea from this film because the right idea does not fit into the 'Darwinian biological principle'. [I'm not one for conspiracy theories and almost didn't write this, but it seems so blatant to me that I felt it had to be mentioned.]

Okay – break over – let's now take a closer look at the various mechanisms discussed in this film and see what we can learn from them. I'll leave random mutations to the end since I'll have the most to say about them.

Nothing New Here

The most important fact to note about most of the mechanisms discussed in this film is that they seem to already exist within the cell. For instance, concerning the various mechanisms that the cell has to destroy or inactivate an antibiotic agent, the video states:

Many bacteria possess genes which produce enzymes that chemically degrade or deactivate the antimicrobial, rendering them ineffective against the bacterium.

In other words, the bacteria already possesses its own antibiotic proof vest. It already has the defense mechanism it needs to ward of the antibiotics. The question is, though, how did the bacteria come to posses these genes that produce these beneficial enzymes? From this film we do not know – no mention is made of them coming about vis-a-vis random mutations or via any other process. They are just there.

The same is true with regards to the mechanism known as Efflux. How did the bacterial cell originally develop this mechanism? Where did it first come from? We don't know – it is, again, just there – a seemingly inherent feature of the cell.

Well, just being there tells us nothing about evolution and how biological organism change or evolve. It does tell us something about how they survive, but we don't just want to know how they survive, we want to know how they obtained their survival mechanisms. And that seems to be as big a mystery to us as ever.

One thing seems clear, antibiotics did not create these mechanisms. They predated the antibiotics – so in these cases antibiotic resistance teaches us nothing about evolution and doesn't even provide any evidence that it happens.

Genetic Transfer

Genetic transfer is far more interesting and potentially relevant to our conversation. In this case, bacteria cells will take on new traits, one's which they didn't have before. But they will get them from other bacteria that did have them before. Again, the resistance already existed in some of the cells – it's just that the bacteria have a highly effective means of transferring that resistance to other cells.

The FDA animation shown above gave a nice introduction to how this works. Here is a slightly more detailed documentary on the process:

With that said, horizontal gene transfer does allow for new combinations of genetic material and does present a manner by which some sort of evolutionary process can take place (although how extensive we do not know). One thing to note, though, is that this is an ordered process – the transfers are not random processes.

Furthermore, we still have no idea where that original resistant gene came from, just an understanding of how they came to spread so quickly in a population. And finally, it's important to note that the means by which this resistance gets spread is NOT natural selection, but horizontal gene transfer. It's a different process which works according to a different mechanism – one which seems built into the way that cells function.

There is much more to say about Horizontal Gene Transfer, beyond what we can cover now. Needless to say, though, it has nothing to do with random mutations and natural selection.

Random Mutations

With that said, let's finally cover random mutations. To start with, I will note that Professor Shapiro clearly states that in the real world bacteria don't become resistant to antibiotics via random mutations – only in the lab (the statement can be found in this lecture – the relevant section starts at 36 mintues, 45 seconds and lasts for a little less than 3 minutes):

[Given that is the case, one wonders why the FDA did not mention this in their film and why they placed random mutations as the first mechanism that they discussed.]

Either way, there is another problem with random mutations as a source of evolutionary change – as this video points out:

So there are a few problems with the mechanism of random mutations plus natural selection being the vehicle by which bacteria evolve.

For starters, as David Berlinksi put it, no matter what we do, bacteria stay bugs (starting at around 3:32, although the whole video is worth watching):

In other words, we can't produce or observe the radical changes needed for evolutionary theory.

Secondly, it is not clear how well random mutations can survive in the long run – and evolution is a long-run theory (it doesn't need to just provide a temporary change, but one that can contribute to a long evolutionary process).

There is a third point, one made by Lee Spetner in his book Not By Chance. This is a more technical point about how random mutations lead to loss of biological information and the problem this creates for the theory of evolution. This is a somewhat technical point which requires some background information. Hopefully I'll get a chance to cover it in the future, in the meantime, though, you can read his book to learn more.

Where Does This Leave Us

At the end of the day, it seems to me that antibiotic resistance offers little if any evidence for the theory of evolution with the caveat that horizontal gene transfer opens up a whole new question of how biological changes take place. Still, in our case of resistance to antibiotics it doesn't seem to be the source of resistance.

And so we are left basically right where we started. The resistance to antibiotics already existed and we have learned nothing about how or why it came to be there in the first place.

What we have learned, though, is how that antibiotic resistance gets implemented by the cell and/or transferred to other cells. Of course, this is important and useful information. What it is not, though, is the expected outcome of the Darwinian biological principle of survival of the fittest – no matter what that mysteriously inserted voice in the otherwise excellent video by the FDA has to say.

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