Respectful Insolence

ResearchBlogging.orgI’m not sure why, but it’s been a while since I’ve delved into the cesspit of pseudoscience that is the Discovery Institute’s propaganda organ, Evolution News & Views. Perhaps it was because I simply got tired of diving into the depths of stupid. Of course, that then begs the question of why I’ve been spending so much time diving into the Age of Autism website or the sophisticated-sounding yet ultimately vacuously pseudoscientific blather that is David Kirby. Trying to decide which is stupider, AoA or ENV, is rather like deciding whether it would be better to die of cancer or Lou Gehrig’s disease. Both can be horrible ways to go, but in the end you’re still dead, just as in the end your brain risks being rendered dead by reading either website.

Still, I’ve been blogging a lot about antivaccinationists lately, mostly because a lot has been happening, while I haven’t hit on another of my major areas of blogging interest in a while, namely evolution. So, it was with some trepidation that I visited for the first time in a long time that propaganda organ for “intelligent design” (ID) creationism, a variety of creationism that’s too disingenuous and cowardly in nature to show its true colors. However silly young earth creationists can be, at least they come right out and say that they think God did it all. Unlike ID creationists, creationists of the young earth variety don’t hide their true agenda couched in terms of saying some “designer” (who, they solemnly assure you, really and truly doesn’t have to be God but oddly enough seems to resemble strongly the Christian God) did it all.

One thing that ID creationists really, really hate is bacterial resistance to antibiotics, because that is one area of evolutionary biology where evolution and selection can be observed directly and that also has a great deal of relevance to human health and disease, thus demolishing the claims of certain ID creationists that the dreaded “Darwinism” has no relevance to medicine. Sometimes this leads the merry band of creationists at the Discovery Institute to make incredibly ridiculous (and even dangerous) recommendations about treating bacterial infections. Particularly difficult for them to understand is that the existence of multidrug resistance, be it in cancer or bacteria, is not evidence against “Darwinism.”

They’re at it again (or maybe I should say that Jonathan Wells is at it again), abusing a new scientific article in a vain attempt to show that it supports ID rather than “Darwinism.” The article is entitled The Irrelevance of Darwinian Evolution to Bacterial Resistance, which is launched in response to a recent article by Maurice et al1 about the mechanism of multidrug resistance in bacteria. As unbelievable as it sounds, I think that Wells is trying to out-stupid David Kirby, and that is simply begging for a dose of –well, you know what kind of insolence.

It’s fairly obvious right from the start that Wells didn’t read the actual article itself but rather skimmed the press release about it looking for statements to inflame him, which is not too difficult. (Apparently, all you have to do is to say that evolution is the driving force behind the emergence of antibiotic resistance to get him all riled, and he doesn’t disappoint:

Frédéric Dardel and his colleagues crystallized two forms of the antibiotic-modifying enzyme acetyltransferase and showed that it has a flexible active site that can evolve to enable bacteria to break down various antibiotics and render them useless. The research may aid in the design of new antibiotics to deal with this form of resistance, which is becoming a serious medical problem.

This is very good news! Unfortunately, Darwinists will probably claim — as they have done many times in the past — that their theory was indispensable to the achievement.

Yet Darwinian evolution had nothing to do with it.

As usual, so confident, so self-righteous, and so just plain wrong. Before I subject my remaining neurons to more of Well’s blather, let’s live up to the icon at the beginning of this post and actually blog about the peer-reviewed research in this article. Let’s, unlike Wells, actually read and discuss the actual peer-reviewed article itself, rather than the press release. I know, I know, it’s a radical concept, particularly to the merry band of antiscientific and anti-intellectuals at the Discovery Institute. But bear with me people. It’s what real scientists in the real world (as opposed to fake scientists in the fake world of the Discovery Institute) do.

As I’ve explained before, the ability to evolve multidrug resistance is a huge problem, be it by cancer cells or bacteria. In the case of cancer, the culprit is usually 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 need for simultaneous mutations in three or more genes, as is sometimes claimed to be necessary by ID advocates, an argument similar to that used by Michael Behe in his most recent book. In the case of bacteria, enzymatic modification of the antibiotic to a form that can no longer bind to its cellular target is a more common mechanism of inactivation. Aminoglycosides (such as gentamycin) and fluoroquinolones (such as ciprofloxacin) are broad spectrum antibiotics. One of the most common mechanisms for the inactivation of aminoglycosides is the addition of an acetyl chemical group to a specific nitrogen, a process known as N-acetylation, a process mediated by an enzyme known as the aminoglycoside 6′-N-acetyl transferase (AAC(6′)). Two functional classes of this enzyme are known, AAC(6′)-I and AAC(6′)-II, each with differen substrate specificity. Now, isoforms of the AAC(6′)-Ib subclass have evolved to be able to modify some fluoroquinolones.

The study in question, by Maurice et al, examined the X-ray crystallographic structure of narrow-spectrum and broad-spectrum variants of AAC(6′)-Ib; i.e. variants that can inactivate only specific aminoglycosides and variants that can inactivate aminoglycosides and fluoroquinolones. What is remarkable about what they found is that a mere two amino acid substitutions can induce a large structural change that allows the binding pocket of the enzyme to accommodate a wider variety of substrates, including some fluoroquinolones. In other words, single residue substitutions can have a huge effect on the function of the enzyme. In other words, teh enzyme has a great degree of plasticity upon which natural selection can work. Moreover, knowledge of the structure of this active site could guide the development of new drugs that could be used with fluoroquinolones or aminoglycosides to block the development of resistance. It’s a nice, elegant little solving of a structural problem that provides a useful new insight into the mechanism of bacterial resistance, concluding:

In addition to the ‘gaping’ ability of the active site, the specific scaffold of AAC(60)-Ib, in which recognition of the acetylatable substrate is mediated by the side chains of the exposed loops (as opposed to other AAC(60) enzymes), could provide the structural plasticity required for adaptation to new antibiotics. This could explain, in part, why this isoform has been selected under the pressure of antibiotic usage and is now widely distributed among pathogens. Conversely, such a broad distribution makes AAC(60)-Ib an attractive target for countering drug resistance. The reported structures could help in guiding the design of new aminoglycosides that avoid resistance. In addition, the observation that an original scaffold–piperazine ethane sulphonate–can mimic the transition state, could be an interesting lead for designing new inhibitors.

And John Wells has to fall all over himself to try to deny that it has anything to do with the hated “Darwinism”:

First, some bacteria happen to have a very complex enzyme (acetyltransferase), the origin of which Darwinism hasn’t really explained. Come to think of it, most cases of antibiotic resistance (including resistance to penicillin) involve complex enzymes, and the only “explanations” for them put forward by Darwinists are untestable just-so stories about imaginary mutations over unimaginable time scales.

As usual, ID advocates like Wells have a lot of nerve accusing anyone of untestable hypotheses and conclusions, given that ID is nothing but one big untestable hypothesis. In any case, the explanations for antibiotic resistance result from testable hypotheses, and evolutionary considerations have revealed more about the mechanisms of antibiotic resistance than any “God did it” (excuse me, I mean “the designer did it”) consideration of ID, particularly resistance to penicillins. Of course, Wells’ critique is so vacuously stupid that I suspect even he realizes it to some extent, which is perhaps why he falls back on favored evolution denialist canards such as this:

Second, the acetyltransferase story is about minor changes in an existing species of bacteria. But Darwin’s theory isn’t really about how existing species change over time. People had been observing those long before 1859, and most of the new insights we’ve gained since then have come from genetics, not Darwinism. Yet Mendel’s theory of genetics contradicted Darwin’s, and Darwinists rejected Mendelian genetics for half a century. And although an understanding of genetics is important when dealing with antibiotic resistance, Darwin’s theory of the origin of species by natural selection is not.

It’s amazing how ID creationists can’t seem to get past the 19th century when discussing science. Remember, the neo-Darwinian synthesis of the 1930s and 1940s successfully combined Darwin’s theory of evolution with population genetics and Mendelian genetics to form the basis of the theory of evolution as we know it today. Moreover, genetics and, more recently genomics, have only served to confirm the validity of the theory of evolution and strengthen its support. Really, ID creationists need to join the 21st century. But Wells’ first two objections pale in comparison as far as cranking the Stupid-O-Meter up to 11 goes compared to his third objection:

Third, Dardel and his colleagues made their discovery using protein crystallography. They were not guided by Darwinian evolutionary theory; in fact, they had no need of that hypothesis.

Wells needs to get a clue. X-ray crystallography is a technique that does not require evolutionary considerations. It’s a tool. However, it is in the the analysis of the data and the conclusions about how the alterations in one or two residues can alter the protein such that it has so much broader a specificity in the antibiotics that it can inactivate where evolutionary considerations are unavoidable. Evolution is the background against which this discovery was made; it allows investigators to predict and understand what mutations might result in a new, more resistant phenotype.

Having read this amazingly predictable and ignorant screed, I’m now reminded why ID creationists irritate me so. They are very much like antivaccinationists in that their beliefs are formed by ideology rather than science and thus cannot be swayed by science. Like antivaccinationists, they attack and downplay inconvenient (for them) science that shows them to be wrong, while twisting existing science into a pretzel in the process.

Maybe I should start perusing the HIV/AIDS denialist websites or the 9/11 “Truther” websites. If I’m going to hurt my brain cells, I should at least do it looking into areas that are will broaden my ability to handle pseudoscience and crankery.

REFERENCES:

1. Maurice, F., Broutin, I., Podglajen, I., Benas, P., Collatz, E., Dardel, F. (2008). Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance. EMBO reports DOI: 10.1038/embor.2008.9

Comments

  1. #1 Eamon Knight
    March 3, 2008

    Of course, that then begs the question of why I’ve been spending so much time diving into….

    Nooooo! That’s NOT what it means! Aaaaaauuuuuuuuugh…….

    (Other than that: great post, and you could have added the BPSDB icon as well — be great to see them both in one post ;-).

  2. #2 J-Dog
    March 3, 2008

    Thanks Doc for doing all the work. Even non-med person like myself can now feel absolute certain that Moonie Wells should immediately turn himself in for a brain scan. Clearly somethings are not operating correctly within his skull.

    If the opportunity presents itself, and if you need some help, I have a Louisville Slugger and an Amana brand Ice-Pick they may prove useful in some exploratory surgery for him.*

    *And since it is well known that IDists have no sense of humor, this is an effing joke! I am NOT threatening to treat Wells to a non-medicated trepanning. Although this would be a GREAT idea!

  3. #3 MartinM
    March 3, 2008

    With newcomers like Egnor and Gonzalez showing up, Wells is clearly trying to reassert his reputation as one of the most dishonest characters in the entire creationist movement.

  4. #4 T. Bruce McNeely
    March 3, 2008

    Given Wells’ education (PhD in molecular biology), I can only conclude that he had sheer contempt for his audience. He must know that he is misrepresenting this study, and doesn’t care because he’s able to “put one over on the rubes”.
    What an absolute creep.

  5. #5 Chuck Darwin
    March 3, 2008

    Nice article Orac.

    Just to let you and other readers know, Kevin Drum over at Political Animal has a very good post up about thimerosal/autism. Unfortunately, the comment thread has started to attract some militia folk (Kelly, for example). As the average reader over there is educated but not a scientist, I encourage everyone to head over and lend their support to the evidence and public health!

  6. #6 hinschelwood
    March 3, 2008

    “Dardel and his colleagues made their discovery using protein crystallography.”

    And analysed the results on a computer which used electricity. Neither the computer nor the electricity have got anything to do with evolution. Therefore evolution is wrong. QED.

  7. #7 jayh
    March 3, 2008

    obviously, since this adaption is “too complex to have evolved”, God knew ahead of time that we would develop these antibiotics, and wanted to be damned sure that we don’t get too healthy. Miserabla bastard that he is, he decided long ago to thwart any attempts to use antibiotics to improve human health. God loves you.

  8. #8 Christophe Thill
    March 3, 2008

    Says Wells (Jonathan, not John) : “in fact, they had no need of that hypothesis.”

    Oh, what a smart little guy ! Mr Wells gives us his version of a little “nudge nudge, wink wink” moment. This phrase is obviously intended in an ironic way. It is Laplace’s reply (or rather, the legendary version of it) to Napoleon asking him where God was supposed to fit in his “System of the world”. Hey, take that now, all you materialist science guys ! A taste of your own medicine !

    Hmm… not that funny, actually, is it ?

  9. #9 Elf M. Sternberg
    March 3, 2008

    I might suggest, Orac, that you go after the Mercury Militia rather than Cdesign Proponentsists because you can see clearly that the ID people are already well-covered by PZ, the PandasThumb, and others, and that there’s already a volunteer army ready to defend evolutionary biology from ideological makeover. The same is not essentially true of vaccination.

  10. #10 Prometheus
    March 3, 2008

    Orac,

    When on the subject of antibiotic resistance, the IDiots repeatedly ask what they think is a rhetorical question, namely:

    “Why did bacteria evolve antibiotic resistance in the first place?”

    There is actually a very simple explanation for the presence in bacterial genomes (and archaeal and eukaryotic genomes) of “drug resistance” genes.

    In the “wild” (e.g. soil), bacteria (as well as archaea and smaller eukarya) are constantly exposed to antibiotics. Fungi, certain bacteria and archaea and perhaps even a few eukarya produce a dizzying array of compounds that they use to kill and maim their competitors (even sometimes members of their own species).

    This “antibiotic war” has been going on for millions of years. It is only very recently that a certain multicellular species has evolved the ability to produce large amounts of antibiotics which it then ingests in order to suppress microbial competitors (and to reign in rebellious members of its own multicellular assemblage).

    Until we (that multicellular Johnny-come-lately to the “antibiotic war”) develop an antibiotic that is truly unique and not simply an analogue of one already in production, we should expect that our opponents will have a counter-measure in their genome (or in a readily accessible genome) that can be “adapted” (i.e. mutated) to anything we throw at them, given enough time.

    Antibiotic resistance – as you pointed out – completely supports evolution (“Darwinism”), despite anything that disingenuous IDiot-based “scientists” might claim.

    Prometheus

  11. #11 txjak
    March 3, 2008

    “Dardel and his colleagues made their discovery using protein crystallography.”

    And analysed the results on a computer which used electricity. Neither the computer nor the electricity have got anything to do with evolution. Therefore evolution is wrong. QED.

    Posted by: hinschelwood | March 3, 2008 11:59 AM

    Bzzt. Nope. Read M. Dardel’s comments on this point: here.

  12. #12 DrFrank
    March 4, 2008

    and fluoroquinolones. What is remarkable about what they found is that a mere two protein substitutions can induce a large structural change that allows the binding pocket of the enzyme to accommodate a wider variety of substrates, including some fluoroquinolones.
    I’m not a biologist, but I suspect that you mean amino acid rather than protein here. Feel free to slap me down if I’m wrong ;)

  13. #13 Andrea Murachelli
    March 4, 2008

    ——
    Wells needs to get a clue. X-ray crystallography is a technique that does not require evolutionary considerations. It’s a tool.
    ——

    Quite the contrary. Protein crystallography absolutely requires evolutionary thinking.

    Many of the methods used in protein production / crystallization and even in phase determination (e.g. molecular replacement) have deep evolutionary rationales behind them.

    Plus, many crystallographers solve yeast proteins in the hope of gaining insight over human ones – clearly something senseless unless you take evolution into account…

    To paraphrase, nothing makes sense in protein crystallography except in the light of evolution…

    Andrea

  14. #14 LuxieP
    March 6, 2008

    I have to ask — how do you manage to read through muck like this daily, and respond intelligently, and not have blood-pressure levels akin to Mount St. Helen’s, circa May 17, 1980?

  15. #15 Karl Lembke
    March 7, 2008

    Interesting choice of words on Wells’ part…

    First, some bacteria happen to have a very complex enzyme (acetyltransferase)…

    Evolutionary biology believes the enzyme came about as the result of natural systems acting in accord with known (or at least knowable) rules. Contrast this with the Intelligent Design / Intelligent Origin Theorists (ID/IOTs) who believe the enzyme “just happened” to be there, by magic or something.

    (I’ll work harder at getting his meaning right when he works harder at getting the science right.)

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.