When I was growing up, my family was deeply religious, and they had some interesting beliefs. We had a book at our house, for example, entitled “Dinosaurs and the Bible”. I came across the book recently at Amazon at this link — apparently it’s still in print. This short Creationist picture book is aimed at young children and claims the dinosaurs were brought aboard the Ark then went extinct after Noah’s flood. I remember the last page of the book featured a drawing of Tyrannosaurus rex chomping on a watermelon. All animals were vegetarian before The Fall, the book explained; while T. rex’s teeth might look fearsome, they were no more so than those of the fruit bat, and in all likelihood T. rex’s diet was the same.
As a kid, I was taught at home and in Sunday school to regard the theory of evolution as an untruth, a subversive materialist creed which owed more to a social agenda than to science. It wasn’t until I reached high school that I finally discarded Creationism/I.D. altogether. Today I know much more about biology than I did at that time, and the Creationism I was taught when I was young seems crass to me now. In a way, however, it’s interesting, because many of my relatives and a sizable fraction of the American public still believes God created life while the devil created evolutionary biology.
How do you reason with Creationists/I.D. advocates? Sometimes you can’t. They aren’t listening because they think that if they do listen God will be very very mad at them. Some people are willing to listen to reason, however, and I know because I was one of them. So when I talk to Creationists, I like to think back and ask myself, what persuaded me? And for me, the first thing that convinced me the theory of evolution just had to be true was pathogens — killer microbes.
Why pathogens? It’s actually pretty simple, but it’ll be more interesting if I give you an example, so I’d like to tell you a story, the kind of story that I believe will convince anyone with an open mind. It’s about the birth of a serial killer in a muddy river delta — and how a bizarre accident let that killer travel around the world.
In 1817 crowds of pilgrims gathered along the banks of the Ganges to celebrate a three month long Hindu festival called the Kumbh Mela. They came to bathe in the sacred river and wash away their sins. Little did they know its holy waters concealed a lethal surprise.
By September an epidemic of cholera erupted in Calcutta (Kolkata). From there it spread across India as returning pilgrims brought the disease back to their homes. Over the next few years, cholera spread outward from the Indian subcontinent and across the British empire, eventually reaching Europe and the United States.
For many years the nature and origin of cholera remained a mystery. Doctors of the day blamed it on tainted air. It wasn’t until 1883 that German doctor Robert Koch identified the true culprit, a bacterium called Vibrio cholerae. Apparently cholera bacteria had dwelt in the Ganges River delta throughout most of human history, giving rise to occasional local outbreaks that flared up for a while then fizzled out. Rapid transportation and the British Empire enabled them to escape the Ganges and go worldwide.
This much Koch could figure out; but the story of cholera was more complicated than he realized, because most strains of V. cholerae don’t cause disease. In fact, V. cholerae bacteria are actually common in coastal environments around the world. Only a mere handful of V. cholerae strains are actually dangerous to humans.
So here’s the mystery: what happened in the Ganges River delta that turned this peaceful aquatic bacterium into a killer? As it turns out, the best place to look for clues is the genome of the bacterium itself.
Cholera bacteria need two key tools to exploit you. The first of these is a molecule called cholera toxin.
At first glance cholera toxin looks like it’s just one protein, but if you look close it’s actually multiple subunits. One part of the protein recognizes a molecule present on the surface of the cells that line your intestine, triggering a process that unloads its cargo — the A subunit — into the interior of the cell. The A subunit is an enzyme, and it catalyzes or speeds up a reaction that interferes with a signaling pathway inside the cell in such a way the cell is prompted to dump water and salt into the intestinal tract. As countless cells along the walls of your intestines take up the toxin and respond by dumping water and salt, you begin to suffer from severe diarrhea. The loss of water and electrolytes is so rapid it can potentially end in death.
The other mission-critical weapon in cholera’s arsenal is a structure called the TCP. These hairlike threads protruding from the bacterium’s surface enable it to grab onto and colonize the lining of your small intestine where it can rapidly multiply.
Both the cholera toxin and the TCP are encoded by genes located in one of the two cholera chromosomes. If these genes were active all the time, the bacterium would waste a lot of energy. The best scenario for the bacterium is one where these genes are active only at the right time. Changes in the bacterium’s environment activate a protein called ToxR; once it’s activated, ToxR in turn activates the cholera toxin genes and the gene for another protein called ToxT. ToxT in turn activates the genes that code for the TCP. In this way, the bacterium can start producing TCP and cholera toxin once it’s inside your intestine and stop producing them once it’s back in the water supply, where these tools may not be so useful.
If you look closely at the cholera toxin genes, you’ll find they’re different from the rest of the bacterium’s genome in some peculiar ways. It turns out the region containing these genes is actually the genome of a dormant virus, CTXΦ, that became incorporated into the cholera bacterium’s genome. Vibrio cholerae first picked up these genes when it was infected by CTXΦ, and this was a crucial step on the road from aquatic bacterium to pandemic disease. In a way, however, this only deepens the mystery, because the receptor the CTXΦ virus uses to infect V. cholerae is actually the TCP! So V. cholerae must have acquired the genes for the TCP first. The TCP genes are located in a region of the genome called the TCP island which also has some unusual genetic features. It’s been suggested the TCP island may also be another dormant virus, although this is currently in dispute.
If cholera got the ctx genes through infection with a virus, then where did the genes originally come from? We don’t really know, but it’s definitely strange that the sequence of cholera toxin is over 80% identical to the sequence of a toxin produced by certain deadly strains of E. coli. Moreover, the E. coli toxin enters cells and does its dirty work in a very similar way.
It’s also interesting that the TCP and the ctxAB genes are both regulated by ToxR. This couldn’t have been true when they were first acquired by the bacterium, because they were acquired at different times. So this system of regulation must have come about subsequently through mutations in the bacterium’s genome — in regulatory regions of the TCP and ctxAB genes, perhaps.
So here’s what must have happened. At some point V. cholerae picked up the TCP island; later on V. cholerae picked up some version of the ctxAB genes through infection by CTXΦ. Natural selection favored strains equipped with these new tools and also favored further improvements like regulation by the ToxR system, because strains with this genetic equipment could exploit a new niche.
The important thing to bear in mind is that bacteria like V. cholerae aren’t sentient agents; they’re just robots. A bacterium keeps on making copies of itself as long as it can find the resources and energy it needs to do so. Any population of bacteria has some amount of genetic diversity owing to random mutations and also to events like transfer of genes between bacteria (as through infection by CTXΦ, for example). If environmental conditions give an advantage to bacteria that have certain types of genetic equipment, those bacteria will make copies of themselves more efficiently than their competition, and over time the genetic equipment they carry becomes more common in the population. This is evolution in a nutshell, and the rise of cholera illustrates how it can go horribly wrong (from a human point of view). By colonizing your intestine, the cholera bacteria obtain resources they’ll use to grow, and by producing cholera toxin they force you to put them back into the water supply en masse so they can repeat the cycle. It’s also interesting to note that cholera is still changing and evolving — the strains involved in most modern epidemics, for example, are different from the so-called “classical” strains in some interesting ways.
How would a Creationist or I.D. advocate explain all of this? They don’t believe bacteria can develop significant new adaptations, so they’d attribute all these changes to recent surreptitious tinkering by an Intelligent Designer (who is presumably still tinkering with cholera bacteria to make it look like they’re evolving, of course). For the sake of argument, let’s assume for a minute that this unlikely explanation is true. If so, we could deduce at least three things about the Intelligent Designer (possibly more):
1) The Intelligent Designer doesn’t like humans. (Why else would s/he/it design lethal pathogens?)
2) The Intelligent Designer is tricking us by surreptitiously intervening in a way that makes it look like bacteria are evolving in order to fool us.
3) The Intelligent Designer is not very smart. If you were an all-powerful Intelligent Designer that wanted to make bacteria that would kill lots of humans, you could do a much better job, because cholera bacteria don’t survive very well in highly acidic conditions. The vast majority of the cholera bacteria you ingest when you drink contaminated water will perish in your stomach acid. From an evolutionary perspective this makes perfect sense, because we know that cholera became a killer through a blind process of evolution by natural selection. From a Creationist or I.D. perspective, however, it makes no sense at all. Indeed, the only way a Creationist or I.D. advocate can explain cholera is to shrug and say that “God moves in mysterious ways”, which is just dodging the question altogether.
True, there’s lots of evidence for the theory of evolution; so why choose germs like V. cholerae to illustrate? I think they’re compelling for several reasons. In many cases we see pathogens evolving almost right before our very eyes. Take, for example, the rise of antibiotic resistance, which is a textbook case (and one of the first things that made me question I.D./Creationism when I was a teenager). But I also think that pathogens are a dramatic example because they’ve claimed more lives than all the wars in human history combined.
When you think about it in this light, the I.D./Creationist argument becomes even more bizarre. Bacteria like those that cause tuberculosis, bubonic plague and cholera feature adaptations that enable them to invade the human body and get what they need at our expense. To believe in I.D., you have to believe that an Intelligent Designer deliberately crafted these bacteria in this way in the certain knowledge they would cause horrific suffering — suffering on a scale that dwarfs any of the wars we’ve fought in our history. You also have to believe the Intelligent Designer is all-powerful, not very smart and deliberately out to trick us, because I’ll be damned if things like the rise of antibiotic resistance and the rise of cholera don’t look a helluva lot like evolution in action.
So if you are a Creationist or if you believe in I.D., stop for a minute and ask yourself this: What’s the most logical way to explain something like the cholera? or Yersinia pestis? or Mycobacterium tuberculosis? Do you really believe these were deliberately designed in order to kill you, and if so, then why? If you stop to think about it, I believe you’ll find the theory of evolution is by far and away a more satisfying explanation. And once you’ve come to terms with the theory, I think you’ll begin to see it both as a logical explanation for what we see in the natural world and a truly fascinating one as well.
I haven’t really gone anywhere near as deeply into V. cholerae molecular biology as I could — it’s interesting, but there’s just too much to cover in one post. Nonetheless, I’ve kinda summarized what’s important for my argument. If you’re interested, check out the papers below.
 Lipp, E. K., A. Huq, and R. R. Colwell. “Effects of Global Climate on Infectious Disease: The Cholera Model.” Clinical Microbiology Reviews 15.4 (2002): 757-70.
 Shah M. Faruque, M. John Albert, and John J. Mekalanos Epidemiology, Genetics, and Ecology of Toxigenic Vibrio cholerae Microbiol. Mol. Biol. Rev. December 1998 62:1301-1314
 Waldor MK and Mekalanos JJ. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science June 1996: 28;272(5270), 1910-4.
 O’Neal, C. (2005). Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP Science, 309 (5737), 1093-1096 DOI: 10.1126/science.1113398