It’s been a while since I’ve visited the cesspool that is Uncommon Descent, a.k.a. Bill Dembski’s home for wandering sycophants, toadies, and lackeys. There’s a good reason for this; I just get tired of the sheer stupidity that routinely assaults my brain every time I make the mistake of taking a look at UD’s latest attempt to try to refute evolution. Worse, there’s lots of other pseudoscience there these days, from the promotion of the use of cancer therapies that haven’t been subjected to clinical trials yet to anthropomorphic global warming “skepticism.” Yes, every time I peruse the posts at UD, I feel brain cells dying. Now that I’m middle-aged, I’m no longer as blasé about causing the premature death of so many neurons as I may have been as a younger man.
Sometimes, though, a skeptical doc’s gotta do what a skeptical doc’s gotta do, and this is one of those times. Once again, one of the lower-powered intellects in the “intelligent design” (ID) movement (and that’s really saying something) named Gil Dodgen has decided to propose a “practical medical application” for ID in a post entitled, ludicrously enough, A Practical Medical Application of ID Theory (or, Darwinism as a Science-Stopper). It’s proof positive that a little knowledge (and I do mean a little) is a dangerous thing:
Here’s a prediction and a potential medical application from ID theory: Design a chemical or protein which would require a triple CCC to defeat its toxic effects on a bacterium, and it will exhaust the probabilistic resources of blind-watchmaker mechanisms to counteract the toxic effects.
Such a success could and will only come from engineering and reverse-engineering efforts, not from Darwinian theory.
First, I wondered what Gil meant by a “triple CCC.” I assume he means, as Burt Humburg thinks, the Chloroquine Complexity Cluster proposed by Michael Behe in his latest book, The Edge of Evolution, as an example that supposedly shows that there is an “edge of evolution,” beyond which mutation and natural selection cannot produce novelty fast enough to account for the diversity of life. This example has been demolished in detail by Arthur Hunt; so I don’t feel compelled to rehash all of that. It’s also possible that, as Larry Moran thinks, Gil is referring to the more general idea of a selective pressure that requires three mutations simultaneously in order for an organism to survive it. It doesn’t really matter what Gil means; it’s all equally stupid and ignorant, because in reality it is standard evolutionary theory that makes the prediction that using multiple antibiotics would be more likely to prevent the emergence of resistance. Nor is it any challenge to evolutionary theory to postulate that there is a limit to useful mutations; it’s in using bad math and grossly miscalculating what that limit is that Behe and other ID creationists dive into pseudoscience. (Behe’s thesis is so bad that it doesn’t even take a Ph.D. to refute it, as Abbie Smith has so ably demonstrated again and again.)
As a brief aside, I ask: Do you find it irritating how ID creationists appropriate perfectly acceptable predictions made by evolutionary theory and try to convince the ignorant that they are really predictions made by ID? I do.
In fact, evolutionary theory, in concert with other aspects of biology, even suggests to us to large extent how antibiotics should be combined. For example, combining antibiotics with identical or very similar molecular mechanisms of action would be highly unlikely to suppress resistance, because any bacterial mutation that defeats one of these related antibiotics would be highly likely defeat all of them given their shared mechanism. No, what evolution would predict is that, to minimize the possibility of resistance, combination therapy should consist of multiple drugs with very different molecular actions. Such drug combinations are also clinically useful because they often interact synergistically to kill bacteria more effectively, even aside from evolutionary considerations. For example, penicillins work by inhibiting the formation of molecular crosslinks necessary for bacterial wall strength, thus weakening the wall and causing the osmotic swelling and death of the bacteria. (Cephalosporins have a very similar mechanism of action.) Aminoglycosides (example: Gentamycin), on the other hand, bind to the bacterial ribosome and cause the misreading of mRNA, so that the bacteria cannot synthesize vital proteins, while quinolones and fluoroquinolones (example: Ciprofloxacin) inhibit the bacterial enzyme gyrase or topoisomerase, thus inhibiting DNA replication and transcription. These drugs are often paired so that drugs with different mechanisms of action are used, one classic combination being a penicillin or cephalosporin paired with an aminoglycoside.
This concept of combining drugs with different mechanisms of action to minimize the likelihood of the evolution of resistance is not limited to bacterial resistance. Indeed, antiretroviral therapy for HIV is a classic example of how successful this strategy can be. Before the mid-1990s, HIV evolved rapid resistance to single drug therapy with, for example, AZT. However, with the advent of protease inhibitors, it was discovered that it was possible to produce “cocktails” of at least three drugs, which must contain at least two different classes of antiretroviral drugs, usually two nucleoside analogue reverse transcriptase inhibitors plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. As evolutionary theory would predict, these cocktails are far less likely to select for resistant strains of HIV than monotherapy and have led to the enormously increased length of survival in HIV-positive patients, in many cases allowing HIV to be managed as a chronic disease. Unfortunately, as is frequently the case when multiple powerful drugs are taken concurrently, there are side effects; worse, these regimens are often inflexible, requiring carefully timed dosing. HIV is so prone to developing resistance that it doesn’t take missing many doses to give the retrovirus the opening it needs.
Finally, the concept of using multiple drugs to minimize resistance isn’t even limited to infectious disease, such as viral, bacterial, or parasitic diseases. Indeed, it’s a cornerstone of chemotherapy for cancer. One of the most commonly used regimens for breast cancer includes three drugs: doxorubicin, which intercalates itself between DNA helices and inhibits DNA replication; cyclophosphamide results in DNA crosslinking; and taxol interferes with microtubules. GilDodgen preens as though ID creationists were the first ones to have thought of this concept, but in reality it was medical scientists, making real practical use of evolutionary theory and, admittedly, a fair amount of trial-and-error, who put the concept of polydrug therapy to good use. Moreover, this is not a new strategy by any means. Combination therapies, such as the ones I discussed, have been in use for several decades. Even so, it’s hard not to point out to Gil that we still see resistance evolving in bacteria, viruses, and cancer even to combination therapy, contrary to what he apparently thinks that ID would predict.
There are probably several reasons for this, depending upon the specific situation. At the base of it all, though, is probably, as Larry puts it, the fact that scientists don’t yet know every mechanism by which bacteria (or viruses or cancer cells) can develop resistance. Evolution also has a way of bypassing the simplistic sort of thinking that Michael Behe and his sycophant Gil Dodgen invoke when they claim that it is impossible for evolution to produce a CCC-type simultaneous mutation to overcome the selection pressure of multiple simultaneously administered drugs. The reason is that biology tends to be very redundant and thus often not so easily defeated. To demonstrate my point, I’ll start by asking Gil just one question:
Have you ever heard of multidrug resistance?
You haven’t? I’ll forgive you if you haven’t (although if you had done even the most rudimentary Googling of mechanisms of multidrug resistance in bacteria or cancer cells, you would have discovered this mechanism fairly rapidly). It’s a fascinating topic and, among cancer biologists and infectious disease experts, a deadly enemy. Indeed, in cancer, multidrug resistance (MDR) is the primary means by which cancer cells evolve resistance to chemotherapeutic agents. This resistance is due usually to one or both of two molecular “pumps” on the cell surface with broad specificity that are able to actively expel a wide variety of chemotherapy drugs from the cell. The two pumps commonly found to confer chemoresistance in cancer are P-glycoprotein and the so-called multidrug resistance−associated protein (MRP), and mutations in these transporters can allow cancer cells to become resistant to multiple chemotherapeutic agents at once. No “CCC”-like event is required. It turns out that these pumps belong to a family of ATP-binding cassette (ABC) transporters that share sequence and structural homology. As of 2002, 48 human ABC genes had been identified and characterized, divided into seven distinct subfamilies (ABCA-ABCG) on the basis of their sequence homology and domain organization. Drugs that are affected by this method of multidrug resistance include the a drugs with a wide variety of different mechanisms of action, including vinca alkaloids (vinblastine and vincristine), the anthracyclines (doxorubicin and daunorubicin), the RNA transcription inhibitor actinomycin-D, and the microtubule-stabilizing drug paclitaxel, among others.
That’s not the only molecular mechanism by which cancer cells can develop resistance to multiple drugs at the same time. It’s just one of several. But what about bacterial resistance to antibiotics? Unfortunately, bacteria have MDR-like proteins as well, and can also develop multidrug resistance without necessarily having to undergo a CCC-like simultaneous mutation. Indeed, targeting these proteins is an active area of drug development. Once again, it’s a case of evolution being more complex and “clever” than we think. It’s also a case of ID creationists simply being ignorant of basic mechanisms of drug resistance and and the relationship between them in different cells. Indeed, the very fact that MDR-like efflux proteins are conserved between bacteria and mammals would tend to favor evolution, not ID. Finally, using evolutionary theory, it is possible to design clever drug combinations that select against resistance alleles. No ID “theorist” can say the same.
And don’t even get me started on how bacteria can exchange DNA through the process of bacterial conjugation, thus allowing the spread of resistance alleles rapidly through a population.
I was tempted to stop here, having subjected myself to enough stupid for one night and being in a rather merciful mood, but unfortunately GilDodgen couldn’t stop while he was behind. He had to bury himself even deeper:
In the meantime, medical doctors should prescribe multiple antibiotics for all infections, since this will decrease the likelihood that infectious agents can develop resistance through stochastic processes. Had the nature of the limits of Darwinian processes been understood at the outset, the medical community would not have replaced one antibiotic with another in a serial fashion, but would have prescribed them in parallel.
The stupid, it burns. Indeed, the above paragraph is such a hunk a’ hunk a’ burnin’ stupid that I had to step back from my computer screen, lest it scorch my face. Burt‘s done a fine job of describing why the medical community replaced one antibiotic with another over time; I’ll restrict myself to other aspects of this statement.
I would hope that any physician, even an ID proponent like Dr. Michael Egnor, should know that treating all infections with multiple antibiotics “in parallel” is a really, really dumb and wasteful thing to do (and that’s an evidence-based statement). For one thing just adding another antibiotic or two (or three) is not a benign thing; blasting away with antibiotics shotgun-style is likely to do far more harm than good. Indeed, broadening the spectrum of antibiotics used by using multiple antibiotics with different mechanisms of action “in parallel” has a nasty tendency to kill off the beneficial bacteria along with the pathogens, leading to antibiotic-associated diarrhea or even C. difficile colitis, which in extreme cases can progress to the life-threatening toxic megacolon. That’s just one example. There are also the toxicities of the antibiotics themselves (for example the damage to kidneys and hearing that can be caused by aminoglycosides) and the allergic reactions to penicillins. I could go on, but you get the idea.
Worse, using multiple antibiotics can actually lead to more drug resistance. How is this possible, given that I just said that combining antibiotics is a good way to minimize the possibility of resistance? Actually, there is no contradiction. It is true that combining antibiotics minimizes the possibility of resistance evolving–in the bacteria that are sensitive to the antibiotics in the combination, that is. However, whenever physicians combine antibiotics, they also increase the spectrum of bacteria that the combination will kill, leading to “collateral damage” among many other species of bacteria. Given that different drugs kill different species of bacteria with different levels of efficacy, broadening the spectrum of antibiotics will subject species of bacteria other than the one(s) being targeted to antibiotics to which they are not as sensitive as the bacteria being targeted. These other non-targeted bacteria will thus be put under selective pressure to evolve resistance, even as the organisms causing the infection are killed off. Thus, while the targeted organism(s) might not be able to evolve resistance, other non-targeted organisms can. In the case of serious polymicrobial infections, we can’t afford to worry all that much about this consequence if combination antibiotic therapy is what it takes to save the patient’s life, but using, say, triple antibiotics to treat a case of strep throat or an uncomplicated pneumonia, as Gil seems to think we should do all the time, would enormously exacerbate the problem of emerging bacterial resistance to antibiotics.
This is the sort of stuff medical students are taught in the second year of medical school in our basic pharmacology class.
Perhaps you think I’m being too hard on Gil. After all, he clearly never went to medical school, appears never to have taken a basic pharmacology or microbiology course, and clearly knows jack squat about antibiotics, infectious disease, or bacterial resistance. He clearly has no clue that multidrug therapies have been used in medicine to try to prevent antibiotic resistance at least since the 1940s or that combination antibiotic therapy has been a mainstay in the treatment of diseases like tuberculosis and leprosy for decades, just as combination chemotherapy has been for various cancers. (Indeed, some drug regimens for TB utilize three or four different drugs to overcome resistance.) Unfortunately, Gil’s proudly trumpeted arrogant ignorance wasn’t finished at this point. He couldn’t resist adding to it by concluding:
This represents yet another catastrophic failure of Darwinian presumption, which is based on hopelessly out-of-date 19th century scientific naïveté.
“Scientific naïveté“? Gil owes me a new irony meter to replace my old one, which just fried itself into a molten blob of metal and rubber, thanks to the above statement. (He also owes me a new computer keyboard, as I can’t get the Coke his statement led me to spew up out of my keyboard.) The phrase “pot, kettle, black” comes to mind.
ADDENDUM: OK, OK, it’s too easy, but just get a load of this comment by Gil in the comment thread to the question:
Malaria was designed not to be totally cured?
No, malaria was not designed to be capable of evolving to become resistant to anything.
Gee, that “intelligent designer” was one nasty bastard, then, wasn’t he? He/she/it must have “designed” malarial drug resistance from the beginning, then.
ADDENDUM #2: The Panda’s Thumb has a less–shall we say?–insolent response to Gil’s cluelessness that nonetheless utterly demolishes every point he’s tried to make.