I peeked.
I was reading Michael Behe’s new book, The Edge of Evolution, and I was several chapters into it. All he seemed to be saying was that evolution has limits, limits, limits, and those limits are so restrictive that you can’t get from there to here, and he was repeating it over and over, in this tediously chipper narrative voice. Behe insisted that he accepted common descent, though, and acknowledged all this evidence that, for instance, chimpanzees and humans are related by common descent, while saying that it was impossible for them to have evolved naturally from one to the other. So I was getting awfully curious to learn how they were linked by descent while evolution was impossible, and I jumped ahead to the end of the book.
“That can’t be right,” I thought to myself.
Then I flipped quickly through the last chapters.
It’s true. Nowhere in the entire book does he offer a mechanism to resolve this disconnect. He claims things were “designed”, but doesn’t explain by who, how, or when, and doesn’t even give a clear picture of what parts of evolution are designed, and which aren’t. It’s nothing but one long and almost entirely fallacious gripe about the insufficiency of natural mechanisms.
I tell you, it made it terribly hard to go back to where I left off and continue my agonizing plod through the book, knowing that there wasn’t going to be any payoff. There isn’t so much as a forlorn whiff of a hypothesis, not one experimental test, not even a suggestion about what Behe’s colleagues could do in their labs or in the field to use or evaluate his claims—just this unrelentingly negative assessment of most of biology, and this weirdly cocky confidence that he has discovered new mathematical principles that disprove evolution. That really has to be the bottom line in this review, that if you’re looking for a clear statement of the principles of Intelligent Design, it ain’t here.
The only useful information I got out of the book was a realization of just how profoundly peculiar Behe’s ideas about evolution actually are. I’ve read some of his past interviews, and he always goes out of his way to explain that he has no problem with common descent, and that he does believe we can trace our ancestry back to other organisms. I’d gotten the impression that he was some kind of theistic evolutionist, who believes in the general process of evolution, but thinks some kind of designer had to intervene at discrete points in history to shape life in a particular direction. Call me naive, call me confused, but I had no idea how strange Behe’s ideas about evolution actually are.
Behe thinks evolution can manage relatively minor tweaks to an organism; it can refine physiological performance, for instance, and can generate the kinds of variation we see within extant populations. But it is powerless to generate the kinds of change that produce new species or genera (the scope of allowed natural change is unclear). We are all little isolated islands of variation within a sharply delimited range.
But we are all still related by common descent, a term that does not mean in Behe’s hands the same thing that it means to non-creationist scientists. How does that work? The Designer has to explicitly and specifically modify a species to generate a new form. So Homo was sculpted from our last common ancestor with Pan by the conscious intent of an intelligent agent. Actually, every spe… no, it’s not clear what taxonomic unit is the limit, so let’s call them “kinds”…every “kind” had to be conjured into existence by the Designer. I think we can rule out the oft-mentioned idea that he could be talking about intelligent space aliens working as the designers, now—this is a model in which every kind of organism on the planet over its entire history had to be artificially created from its predecessors.
Where is the “edge of evolution”? He has a little diagram to illustrate it.
![i-8ab347c1f1ba2648e68e990222758c51-edge_of_evo.gif](http://scienceblogs.com/pharyngula/wp-content/blogs.dir/470/files/2012/04/i-8ab347c1f1ba2648e68e990222758c51-edge_of_evo.gif)
Everything in solid black is the product of design. Everything in white, that is everything from variation within species to individual mutations, he’s willing to concede to accidental or non-intentional causes. The gray area above species is the edge, where he’s not precisely certain the line should be drawn. That Designer sure has been busy! He’s been working hard to sculpt life on earth towards generating human beings and chimpanzees and malaria parasites, right down to specifying the amino acid sequences of active sites in their proteins. Cells, genes, regulatory networks, all that fundamental stuff is the direct handiwork of a mysterious designer which Behe will leave nameless and unexplored.
As I’ve already mentioned, he’s not going to offer any descriptions or evidence for this amazingly persistent and industrious Designer, so the entire argument is going to rest on his assertion of barriers to variation that cannot be overcome without intelligent aid. Wouldn’t you know it, though—there’s nothing new in his argument, and he mainly just reworks bad old creationist claims about probability.
The centerpiece of his argument in this book is malaria, just as the flagellum was his big evolution-killer in Darwin’s Black Box, and he’s going to make all kinds of sweeping conclusions from a misleading derivation of probabilities in this one organism.
He invents a new metric, the CCC, or “chloroquine complexity cluster”. This is the probability of evolving a fairly simple trait in the malaria parasite, resistance to a compound called chloroquine. Malaria that is resistant to chloroquine has two specific changes to a protein pump called PfCRT; one amino acid at position 76 and another at position 220 are changed from the more common form. By a couple of arguments, from the probability of getting two independent changes in the sequence and the observed frequency of evolution of chloroquinone resistance in the population of infected people, he comes up with a number: the odds of acquiring this specific pair of mutations is one in 1020. Fair enough; if you demand a very specific pair of amino acid changes in specific places in a specific protein, I agree, the odds are going to be very long on theoretical considerations alone, and the empirical evidence supports the claim of improbability for that specific combination.
But now Behe pulls a classic creationist switcheroo. He has one number, a very tiny probability of one in 1020 for one specific result, and he’s going to use this magic CCC value to claim that no significant evolution can have occurred in humans in ten million years of evolution. Not ‘it’s highly unlikely that humans would have acquired this predetermined pair of amino acid changes in a particular protein,’ but ‘no useful pair of amino acid changes anywhere in any of their gene products.’ No, you’re thinking: he couldn’t possibly have said something that stupid. But yes, he really did.
No mutation that is of the same complexity as chloroquine resistance in malaria arose by Darwinian evolution in the line leading to humans in the past ten million years.
Wait…so complexity is the same as improbability? He goes even further; he argues that no CCC equivalent arose in the entire order of mammals over the entire span of their existence.
Mammals are thought to have arisen reptiles and then diversified into a spectacular array of creatures, including bats, whales, kangaroos, and elephants. Yet that entire process would—if it occurred through Darwinian mechanisms—be expected to occur without benefit of a single mutation of the complexity of a CCC. Strict Darwinism requires a person to believe that mammalian evolution could occur without any mutation of the complexity of this one.
Whoa.
Behe is basically arguing for the special creation of each and every mammalian form; that although the designer worked by modifying existing stocks, he/she/it had to go in and specifically add in every unique, complex attribute that distinguishes one from another, right down to different levels of resistance to species-specific pathogens. Behe isn’t just a crackpot who thinks he has a novel explanation for an evolutionary mechanism—he’s a radical anti-evolutionist extremist who rejects the entire notion of the transformation of species by natural processes.
Yet his argument for this dramatic conclusion is not only weak, it’s wrong. I could, for instance, correctly argue that the odds of getting a straight flush dealt to you in a 5 card poker hand is about 1 in 6×104; we could calculate this with probability theory, and we could also deal lots of poker hands and determine it empirically. No one’s going to argue with that part of the math.
But now, if I were to define a Straight Flush Complexity Cluster (SFCC) parameter and wave it around and claim that “no hand of the same complexity as a straight flush has been dealt by chance in the last ten years of poker games here in town,” that players can only possibly win one hand in 60,000, or worse, that no one has won a poker hand without cheating and stacking the deck, you’d know I was crazy. But that is basically Behe’s entire argument — he claims to have found the “edge of evolution,” and that it is much sharper and steeper and more impassable than anyone but a creationist could believe.
One more problem: he’s dimly aware that there might be some weakness in his argument along the lines of what I just explained, and he dedicates one whole paragraph to trying to plug the hole. He argues that many mutations occur in the malaria genome, and that there is so much churn that “mutations in all of the amino acid positions of all of the proteins of malaria” can be expected to occur by chance, yet only these two particular changes have been so far found to confer chloroquine resistance. It’s an admission that the target for this particular solution is very, very narrow within the search space of the genome of the extant malaria parasite. That’s fine, I can see that, but it doesn’t address the problem with his generalization: it does not mean that the range of solutions to all problems in evolution are similarly so tightly constrained, yet he is pretending that they are. He doesn’t understand that I don’t need to get a straight flush to win every poker game; sometimes a pair will do. He also doesn’t seem to understand that, just as in many poker games I can discard and draw, so too in evolution we can take an incremental approach: a single mutation that helps a little bit may be retained and promote the fitness of a lineage until a second mutation can improve it yet more.
That’s just the third chapter, where Behe argues for “the mathematical limits of Darwinism” on specious grounds. The whole book has this same problem of tired old creationist arguments spruced up with pseudoscholarly language. Mark Chu-Carroll has really shredded this part of the book, and also deals with the amazingly incompetent mish-mash he has made of the concept of adaptive landscapes; ERV has run with that and shown that Behe’s idea of how landscapes work is a cartoon version of reality. Nick Matzke has an interesting discovery: Behe also continues to tout the cilium as an example of irreducible complexity, but Nick discovers a prime example of reduced complexity of the cilium…in the malaria parasite. This book keeps pounding away at that plasmodium, you’d think he’d have noticed.
I think you can expect many more such dissections that expose the rank incompetence of this book. Most of the arguments are gussied up versions of the kind of handwaving, ignorant rationalizations you’d get from some pomaded fundagelical Baptist minister who got all his biology from the Bible, not at all what you’d expect from a tenured professor of biochemistry at a good university—throwing in an occasional technical gloss or mangled anecdote from the literature is only a gloss to fool the rubes.
This has only been a too-long dismissal of one of the early, obviously fallacious points in the book. And because it’s too long, I’m going to stop here for now—next, I want to jump ahead and focus on one chapter. Chapter 9. “The Cathedral and the Spandrels.” In that chapter, Behe tries and fails to dismiss all of development and evo-devo of having any significance in understanding evolution, and goes after Sean Carroll and Eric Davidson. Trust me, he does an even worse job of that than he does in trying to dismiss all of evolution on the basis of the probability of two amino acid changes.
Several people have pointed out that his calculation of the frequency of evolution of cloroquine resistance seems dubious. Here’s his rationale.
The mutant PfCRTs exhibit a rang of changes, affecting as few as four amino acids to as many as eight. However, the same two amino acid changes are almost always present—one switch at position number 76 and another at position 220.
…
Since two particular amino acid changes occur in almost all of these cases, they both seem to be required for the primary activity by which the protein confers resistance.
… [several pages later]
…resistance to chloroquine has appeared fewer than ten times in the whole world in the past half century. Nicholas White of Mahidol University in Thailand points out that if you multiply the number of parasites in a person who is very ill with malaria times the number of people who get malaria per year times the number of years since the introduction of chloroquine, then you can estimate that the odds of a parasite developing resistance is roughly one in a hundred billion billion.
That’s it. That’s the entire rationale. It’s very poor, and even granting it to him, it’s still not applicable to the whole problem of evolution.
Behe is basically arguing for the special creation of each and every mammalian form.
I might accept the special creation of the platypus, but that’s about it.
. . . No, no, not really. Yeesh, Behe’s a jerk.
Added to the list. . . .
Thanks for the review PZ. I also asked Mark this question, but want to get it clear in my mind. Is Behe seriously arguing that in the last few decades, God has been actively producing chloroquine resistance in malarial parasites?
What about observed instances of speciation – has God been acting in these cases? What about speciation observed in laboratory experiments – did God sneak in under the noses of scientists and do it whilst they were out on a coffee break?
It seems like he is basically more anti-evolution than YECs.
“He claims things were “designed”, but doesn’t explain by who, how, or when, and doesn’t even give a clear picture of what parts of evolution are designed, and which aren’t.”
The Edge of Evolution: The Matrix Revolutions of ‘intelligent’ design.
“One more problem: he’s dimly aware.”
Full stop.
Fixed it for you, PZ.
Let me know if my thinking is correct here.
He also seems to be not realizing that if malaria hadn’t developed that mutation it would have gone extinct. And then there would have been some other life form with some mutation for him to point to and saw how improbable it is. That anything close to correct?
From your review it seems that Behe’s probability argument is simply ignoring (or ignorant of) the fact that what occurs in nature are populations of organisms with large numbers of individuals over time. Is it really that simple of an error on his part?
So, would this waste of cellulose even worse than Behe’s “Darwin’s Black Box”?
No, he’s saying that mutation and selection do generate chloroquinine resistance, but that it’s an extremely low probability event that requires huge populations and many generations, and that if you remove the selection pressure of cloroquinone they quickly slide back to the native state. Basically, he’s saying that this marks the absolute limit of what evolution can do, and it isn’t much.
I suspect that in the observed instances of speciation, he’d say that those simply aren’t “complex changes” — he allows for a narrow range of permissible variation that could include anything anyone might offer to counter his assertion. He’s just rephrasing the micro/macroevolution distinction that so many other creationists do.
YECs are nuts. I don’t think he’s more nuts than they are, he’s pretty much at the same level of nuttiness. He’s just had training in how to mumble nutty things with the lexicon of science.
Not the mention of course that apparently God is directly responsible for the creation of drug-resistant malaria.
Apparently Behe argues for a malevolent God.
Yeesh. I’m impressed he managed to squeeze so much falsehood and misrepresentation into a single diagram.
I’m also getting pretty tired of the fine-tuning two-step. First, you say that the laws of nature are cunningly devised so that life may arise, and then you say that it’s impossible for life to do anything. Which is it: a hospitable universe or an inhospitable one? And if the history of life is so improbable that it could never have happened naturally, why don’t we see physical laws and constants of nature so hostile to life-as-we-know-it that such life as ourselves could never arise? Conversely, if the fundamental principles of physics and cosmology were so well chosen that life of our kind was possible, or even perhaps inevitable, why couldn’t the mechanisms of genetics perform equally well?
The whole argument is incoherent; its only saving grace is that it is also wrong. As Sean Carroll once wrote,
So how improbable is the mutation that causes my eyes to bleed everytime I read the word ‘kinds’ in a creationist context?
Brian: Not exactly. He’s saying that the empirical evidence seems to demonstrate that there are relatively few ways for Plasmodium to develop chloroquine resistance — it’s a haystack with one small needle. That might be reasonable. What isn’t reasonable is that he then draws the unwarranted conclusion that no haystack could contain many needles, or that evolution might have mechanisms that allow hidden needles to be easily exposed.
Shaggy: No, that’s not his point. He concedes huge numbers and many generations. What he claims is that all evolutionary solutions of any significance are so “complex” (by which he means improbable) that there hasn’t been enough time to generate them.
Stanton: YES. Much worse. And that’s saying a lot, since I considered DBB to be a flaming piece of shit.
Blake Stacey wrote: “Why do the constituents of nature exhibit this pointless duplication, if the laws of nature were constructed with life in mind?”
Or, as someone once pointed out on Skatje’s blog, the universe was evidently designed for dark matter, since that is evidently the most common substance out there…
Fascinatingly crazy stuff. One more question if I may. How does he deal with transitional fossils? So, in the case of the tetrapod series, was God creating a fossil series that pretty much looks what you would expect from evolutionary processes. He poofs Panderichthys into existence, then Tiktaalik then Acanthostega? His grand plan is to create lovely transitional series and the occurrence of common descent?
Thinking along similar lines, what about humans. He accepts (in his own idiosyncratic way) common descent for humans, does that mean that he created Homo ergaster, then Homo heidelbergensis before finally bringing us about? Why on earth would this happen? Why not just poof us straight into existence, why the need to toy around with prior intermediary steps.
This book raises so many questions about where Behe is coming from. It’s so deliciously confused I hardly know where to start.
Not to nitpick, but I think you got the odds of getting a straight flush incorrect.
With 52 cards in a deck and five cards chosen at random, there are (52 C 5) = 52! / (47! 5!) unique hands (assuming order doesn’t matter), of which 36 are straight flushes (4 suits, 9 straight flushes per suit). According to my calculations, that comes out to 1 in 7.219 times 10^4.
1 in 6e4 is close, but I just had to check — I tried for days to teach my HS class that calculation!
Ok, I’m seriously confused… his chart says evolution can create variation within a species, then he spends the rest of the book arguing that it can’t? Is that what he’s actually saying?!
gg:
Heh heh heh. Who was that mysterious masked meddler who quoted Carl Sagan —
And then said,
At some point, I should write up the history of dark energy and suchlike. It’s an interesting development, and sadly, the popularizations of cosmology from before 1998 are out of date.
Fewer teens actually play cards these days, so it’s starting to fail as a mnemonic for teaching probability.
I suppose people play solitaire online, but I think there is something lacking in the tangibility of it.
Blake wrote: “Heh heh heh. Who was that mysterious masked meddler who quoted Carl Sagan…”
I had my suspicions, but was too lazy to go back and find out. All that pointing-and-clicking…
It would be nice to see an up-to-date history of the dark matter/energy question. The last thing I heard about was the ‘direct’ detection of dark matter via colliding galaxies, but that was overshadowed in the news by the much more scientifically important question of Pluto’s planethood.
Spudbeach:
Er, there are ten straight flushes per suit. I suspect you’ve neglected the “wheel” straight (A-2-3-4-5).
I’m too lazy to work out whether that reconciles your calculation with PZ’s.
Regarding the “chloroquine complexity cluster”, clearly this idea has some very interesting theological implications. If chloroquine resistance is not a result of evolution, but rather the recent handiwork of an active deity, then God must really, really the people of West Africa — particularly children, the elderly, and people with compromised immune systems. What a fucker…
Uh-oh — that chart Behe made, where he explicitly shows what comes out of accidental or unintentional causes, lists “individuals.” God did not specifically have anything to do with planning individuals. He doesn’t intervene on that level.
Does that mean that we were not created lovingly by God for a purpose? We’re all just cosmic accidents, because all He cares about is the “kind?” Moms and dads just happen to meet, we just happen to be born.
Behe is taking away Meaning. Meanie.
Heretic.
He doesn’t deal with transitional fossils, and they aren’t a problem for him. This is a hypothesis of continuous creation. Each of those fossils represents a species that was specially created by the designer.
hehehe How many people on SciBlogs, a very small subset of ‘scientist’ population, directly research the stuff in the ‘black’ bar. lol! Punching the face of Gawd, the lot of ya! Oh wait! I mean The Designer!
Shoot.
Maybe I have a twisted view of things, with HIV, but impossible mutations happen every day, in every HIV patient. Every day. Not billions and billions of years. It would be my hypothesis that the appropriate mutations for CCC (whatever) have happened multiple times over the course of malarias natural history. And it only needs to have happened once in modern history to spread exponentially through our population.
I mean ‘odds’ of ‘CCC’ would only matter if you thought ‘CCC’ evolved independently in every ‘CCC’ patient?
Ek I really dont know how you all are slogging through this book.
If everyone in the world was given a lottery ticket, then each person would have a one in six billion chance of being a winner. That is such a small chance of winning that we must assume that the only way any person could win such a lottery would be through divine intervention.
Is that something like the argument he is using?
gg:
Did you hear about the dark matter “smoke ring”?
A classic Modesty Blaise-Willie Garwin tactic in a tight spot is the “high-low switcheroo”. (One reverses high and one reverses low to surprise surrounding attackers.)
But this is a low-brow switcheroo. And don’t get me started on how it places Behe in a tight spot.
But Behe is a slick flaggelical Creationist minister; I’m not sure I would expect much of a difference.
Yes, or to paraphrase Kronecker, evolution created 10 fingers, all remaining numbers is the work of man.
Actually, I think the possibility of the landscape drives some of the more educated creationists crazy. The string landscape may have 10^500 different solutions, which is a bit more constrained than the infinity of possible vacua of field theories, but it is still way more nature given possibility than they like.
A classic Modesty Blaise-Willie Garwin tactic in a tight spot is the “high-low switcheroo”. (One reverses high and one reverses low to surprise surrounding attackers.)
But this is a low-brow switcheroo. And don’t get me started on how it places Behe in a tight spot.
But Behe is a slick flaggelical Creationist minister; I’m not sure I would expect much of a difference.
Yes, or to paraphrase Kronecker, evolution created 10 fingers, all remaining numbers is the work of man.
Actually, I think the possibility of the landscape drives some of the more educated creationists crazy. The string landscape may have 10^500 different solutions, which is a bit more constrained than the infinity of possible vacua of field theories, but it is still way more nature given possibility than they like.
The black bar in the diagram is the Gap, the one where the God of the Gaps lurks. The gray bar is where the Gap has been shrinking. The white bar is where the Gap has already retreated from.
Oh, and, PZ, are you a closet entomologist? I’d love to see a classification that contained “the entire order of mammals”! Would be a nice change. :o)
The black bar in the diagram is the Gap, the one where the God of the Gaps lurks. The gray bar is where the Gap has been shrinking. The white bar is where the Gap has already retreated from.
Oh, and, PZ, are you a closet entomologist? I’d love to see a classification that contained “the entire order of mammals”! Would be a nice change. :o)
Torbjörn Larsson, OM:
And somewhere else in that landscape is a D2-brane populated by Flatlanders, whose pentagram-shaped scientists are trying vainly to convince the smug, self-satisfied circles of the priesthood that universes of three dimensions could contain intelligent life.
I just feel sorry for his unfortunate Lehigh colleagues. Both for the damage he does to their department’s reputation, and for what I suspect is the trial of having to put up with him personally. They must be wondering, all these years, what they’ve done to deserve such punishment.
Spudbeach and Rieux: I’m not a statisticain, but the fact that the ace goes with the high straight or the low straight requires an extra adjustment in your equation because in the same hand in the same suit, you can’t have BOTH a high and low straight.
ERV:
Could we perhaps say, “HIV experiences six impossible mutations before breakfast”?
What astounds me is that Behe even settled on this probability argument in the first place. It’s a classic canard, and he could have found all the points PZ raises in an hour’s worth of websurfing.
Jeez, if the Designer has to sign off on every single speciation event, She must have been really busy with Hawaiian fruitflies. And what IS with all those beetles? It’s really amazing that anybody’s prayers about football games and lottery payoffs and miraculous cancer remissions EVER get answered.
But don’t you see? Evidence suggesting He did not fine-tune the universe just shows how ineffable He is and how mysterious His creation is. Evidence that the universe is not designed is actually evidence that the universe really is designed.
And, yes, I have seen creationists using pretty much this exact argument. On this very blog, I think.
Are the items in Behe’s chart in any particular order? I’m particularly interested in this string:
Integrated protein networks
Phyla
Cell types
Classes
Could someone more schooled in taxonomy and biology explain that string to me? Does one thing really follow from another there or is Behe just listing things randomly. (and what are the chances that THIS random string would appear?)
That really has to be the bottom line in this review, that if you’re looking for a clear statement of the principles of Intelligent Design, it ain’t here.
Sure it is. Intelligent Design: They don’t come from no stinkin monkeys.
Urr. Let’s check his math, here. Say the mutation rate in Plasmodium is 1e-8 per base pair per generation, which is pretty reasonable. We want a particular substitution, so the odds of getting that are 3e-9 per base pair per generation. We’re interested in two very particular substitutions, meaning our odds are 3e-9^2 or ~1e-17 per generation. This is 1e3 off from Behe’s number, but let’s assume it’s okay. To be clear, these are the odds for a SINGLE DIVISION of plasmodium. During acute infection, parasite count can be extremely high (as high as 1e6 per microliter). Let’s say its maximum count is 1e4 per microliter, which is reasonable. So in a single individual this could be 1e4 * 5e6 parasites total, or 5e10. This already brings our odds of acquiring this particular mutation to in the range of 5e-7. Now let’s imagine ~1e5 people getting treated with chloroquine a year, and our odds of this particular mutation arising in a chloroquine resistant individual in a single year are 5e-2, or 5%. Those are not long odds.
Next?
Rieux,
I’m with spudbeach.
I only make 9 straight flushes per suit, plus one royal flush. Unless you’re saying that a royal flush should be counted? I think it’s something else…
Millimeter Wave:
Er, what? A straight flush is five cards of the same suit that are both a straight (five cards of sequential rank) and a flush (five cards of the same suit). Which part of that definition does a royal flush not satisfy?
No, a royal flush is merely the highest ranking straight flush. They’re not separate categories–any more than “pair of aces” is a separate category from “pair.”
How in the living hell does he come up with that number? If he is talking about the probability for two simultaneous amino acid changes, given a mutation rate of 10^-9 per nucleotide per generation, and assuming two nucleotide changes, the chances are 10^-18 in any given individual in any given generation. That’s already lower than Behe’s estimate. A large infection contains something like 10^11 parasites. If you have a million infected individuals, you’re going to get one double mutant like this in every generation. And generations go by pretty fast for Plasmodium.
All I can figure is that he’s assuming more than two nucleotide mutations in order to get the double mutant. But here’s the problem. Chloroquine resistance is caused by the mutation K76T, which requires only one nucleotide change. THIS CHANGE ALONE IS SUFFICIENT FOR CHLOROQUINE RESISTANCE! The other mutation, while presumably helpful, is not necessary for selection to kick in. The changes can therefore occur stepwise.
If you think that’s bad, it gets even worse. K76T is not the only mutation at that site that confers chloroquine resistance. K76I and K76N do so as well. So not only is there only one nucleotide change required, there are a variety of various changes that can do the trick.
It’s looking like Behe really, really, really screwed himself on this one.
There is much more variation in PfCRT sequences than simply at positions 76 and 220. In clinical isolates collected over the past 50+ years, mutations at at least 16 positions in PfCRT have been discovered (see Trends Pharmacol Sci. 2006, Vol 27 pp.594-601). Attempts to introduce the K76T mutation by itself into sensitive parasite strains have in fact failed in the laboratory, which might suggest that it seriously hampers the function of the protein. However, if multiple (16+) mutations could compensate for that, in multiple combinations, then the odds of K76T arising naturally are shortened even further than if 220 alone were a precondition.
It could be argued that the historical use of quinine to treat malaria by indigenous populations may even have contributed to the genetic diversity of PfCRT, as quinine pressure appears to favour mutations at further sites in PfCRT (Mol Microbiol. 2007 Vol 63 pp 270-82.
And guess what? Although it is a strong predictor of chloroquine resistance, it surely is not the only protein involved, as several studies on a multi-drug transporter, PfMDR, have shown, to name but one example. If other proteins can contribute to chloroquine resistance too, then there’s even more chance for PfCRT and other genes to cross their ‘neutral gaps’ in order to produce significant resistance in a strain. Not only that, but the K76T mutation isn’t even present in all chloroquine-resistant isolates.
I find it ironic that in order for his argument to make sense, Behe has to over-simplify the very complexity that he says shows design, when in fact the complexity allows the opposite, probably with room to spare.
This bothered me also. It seemed screwball wrong.
I don’t know much about the nuts and bolts of chloroquinine resistance. But in general, resistance mutations can be sequential and additive or synergistic, not necessarily simultaneous.
By sequential, partial resistance would be 10exp-9. Further selection on the step 1 pool would be 10exp-9. In this case, the probability of ending up with a double mutant would be 1 in 2X10exp-9 not 10exp-18. If anyone knows anything about this, feel free to check my reasoning. But I’m not seeing Behe’s reasoning at all.
At this point, I think that we can conclude that there is a vast gulf between Michael Behe and Ken Miller.
Wait a minute… So he’s saying that humans do come from apes? Isn’t this the same ridiculous, untenable, awful, godless claim creationists oppose? How come they’re championing Behe?
Wait a minute… So he’s saying that humans do come from apes? Isn’t this the same ridiculous, untenable, awful, godless claim creationists oppose? How come they’re championing Behe?
The gulf gets even bigger. Now the DI is unhappy because those nasty Catholic Thomists are, how shall we say, unenthusiastic about ID.
:)
saurabh
thank you for doing the math along with the Plasmodium life history. This really is a case of Behe being ignorant (or willfully ignoring) the large number of individuals in the Plasmodium populations over time.
I’ve added the bits from the chapter on how he estimated that getting two specific mutations in a protein has odds of 1 in 10^^20 to the end of the article. You’ll see it’s rather … tenuous.
Thanks PZ. That extra part really doesn’t make much sense. The only thing I can think is that he doesn’t realise that resistance doesn’t have to develop de novo in each infected human; infected resistant parasites can of course be sucked out by the next mosquito bite, and transferred to the next host. Only one individual could be responsible, as the mosquito carrying the resistant parasites can infect many people. The fact that resistance appears to have developed independently in 10 different places surely shows that it is more likely than not, given that it only *had* to evolve once?
I think I found the article Behe cites in that last quoted passage — Nicholas J. White’s “Antimalarial drug resistance” J. Clin. Invest. 113:1084-1092 (2004). It’s available for free online.
Oops. I hit “Post” too soon. The following paragraph of White’s article suggests that (a) mutant P. falciparum with chloroquine resistance are less fit than their non-mutated cousins in the absence of chloroquine, or (b) the host’s immune responses eliminate mutants we would otherwise see, making the in vivo rate much lower than the in vitro.
(If I can parse the jargon correctly, that is.)
Here is how Behe gets the 1 in 10^20 number:
p. 57:
The relevant notes on p. 281:
If you read the key paper, White 2004, you see only:
I see nothing explicit in Su et al. 1997 about less than 10 origins, or a 1 in 10^20 probability. This is probably what White was looking at:
Apparently the resistance allele is the Dd2 allele of the cg2 gene. But Su et al. 1997 suggests recombination, which of course Behe never mentions:
This is pretty thin gruel on which Behe bases his 1 in 10^20 estimate for the origin of chloroquine resistance, which is used throughout The Edge of Evolution!
Behe says on page 59,
He doesn’t even know if it really is two mutations that are necessary to cause chloroquine resistance! It might be several mutations for all he knows, or it might just be that the number of different resistance events detected by researchers in the wild is much smaller than the number of resistance events that actually occur (consider the filters: 1. Not all beneficial mutants survive, many will die in their host; 2. Many beneficial mutants will lose out in the race to “selectively sweep” the population; 3. Researchers will mostly only detect the few mutants that have successfully swept to a large proportion of the regional population). Or it could be that the rare event is a recombination event or something else.
And yet CQ resistance by the (assumed!) “double mutation”, with probability 1 in 10^20, is Behe’s central measuring stick throughout the book! Incredible…
PS: Now, looking at the literature:
(Behe cites this paper as ref #1 of Chapter 3 but apparently ignores its discussion of how malaria evolved.
So it looks like resistance actually occurs by the gradual accumulation of several mutations, and that what you are seeing in the wild is not a few rare double-mutation events, but instead a few much-evolved strains that have accumulated a large number of resistance mutations.
PPS:
From Chen et al. 2005. So A220S, which is one of Behe’s required chloroquine resistance mutations, is not actually required. (I should add that Kenneth Miller tipped me off to this.)
PZ says:
Yet his argument for this dramatic conclusion is not only weak, it’s wrong.
Actually I think the phrase ‘not even wrong’ applies. Unfortunately it seems that Behe has lost touch with reality and reason.
Merci mille fois, M. Matzke!
:-)
The point about “consider the filters” had occurred to me, too, although I’m far from a professional in this field. Just before I saw your comment here, I mentioned it at Aetiology, so you might want to post your comment there, too.
Rieaux, op99 and millimeter wave:
I stand corrected. Whenever I have played poker, I always counted the ace as high in a straight, and disallowed all wraparound straights (including 5-4-3-2-A). After a quick check of wikipedia, I find I was mistaken. With that correction, the odds of a straight flush in a single 5 card hand (no draws) is 1 in 64974, within PZ’s implied error bound (40 possible straight flushes, 52 C 5 = 2598960 possible hands).
And yes, millimeter wave, that includes a royal flush as a straight flush.
Now, back to the subject: do you think Behe has had anybody going over his calculations with a fine tooth comb? I doubt it. And if it’s this easy to be off when calculating poker hands, how easy is it to be off calculating odds way beyond the limits of intuitive calculation?
OK, spudbeach, now I want you to give back all that money you won off your poker partners.
You could’ve saved yourself the time and keystrokes by simply printing the review thusly:
“Behe makes the standard arguement from personal incredulity. The End.”
Not that I blame you for ranting. If you don’t get it out here, you’ll just take it out on the grad students and we can’t have that. (Although you can sacrifice a few undergrads since they’re a dime a dozen)
I’m just wondering how Behe dares to come up with numbers for probabilities for anything at all, after the Dover trial, where he got caught under oath… Search for ‘soil’ on http://www.talkorigins.org/faqs/dover/day12am.html
I’ve wondered quite a few times how Behe can reconcile his acceptance of common descent with his dismissal of any natural mechanisms that can account for it. For example, he claims to accept that humans and chimps had common ancestors but his CCC example clearly shows that he rejects the possibility that this could occur in the absense of “intervention”. Seems to me that he accepts common descent only in the sense that things reproduce.
Hawks – Maybe he accepts common descent by thinking that the Designer used the same “pattern” of chimps for humans – that is, the Designer did not create humans from scratch, but took just a bit of this and that from the chimps and added something else to make them human. Or else that there was a basic mix (sort of like Bisquick) that the desiger could use to make pancakes (apes), waffles (chimps), or biscuits (humans). They all have the same basic ingredients, but also little differences and then you mold them differently. Not scientific, but then . . .
this surprises you?
didn’t you read “darwin’s black box?” that was one of the major and obvious flaws with that book. it’s more like “behe’s black box,” the box being god. no mechanism, just magic. poke some (imaginary) holes in evolution, and conclude that this proves god did it. and assume that this outcome is so obvious that you don’t actually need to say anything more. after all, that’s why everyone read it — for justification of god’s perfect poofing plan.
that’s all kinds of fallacies.
BC,
I appreciate that he MIGHT mean something along those lines, but I doubt it. The people at uncommondescent sometimes use the phrase “common design” to refer to such concepts and I doubt that Behe has never heard of that expression. IF Behe is that confused then it would also mean that he thinks that aeroplanes and automobiles share common ancestry. I know he is no biologist but, come on…
All this talk of complexity, complexity, complexity. And then probablities!
If I hadn’t already realized that the whole idea of God is hogwash, this alone would have turned me into an atheist.
The way I see it, this universe is so very complex, no matter from what angle you view it, so chaotic, so multi-layered, so inter-twined, so changeable, that any conscious, intelligent act of planning it would take a measure of thought many times greater than the number of particles in it multiplied by the number of nano-seconds it has endured.
(Mankind cannot even think of such a being; all we do is extrapolate until the numbers are too big for us, then say, “God is great!” and have done with it.)
Whereas unthinking forces, acting on barely-there bits of matter, helped along with a handful of more-or-less self-replicating bits, accounts quite nicely for the increasing variety that we find. And, although the details escape us, at least the mechanism makes sense.
So Behe admits that we know resistance alleles don’t always have to involve these two mutations, but since he throws in the word “primary,” he never has to think about this fact again!
It’s very funny seeing Behe use his calculations to prove that evolution can’t happen, is too improbably to happen, almost never happens… and meanwhile it’s going on all around him. If God is deliberately overriding the probabilities by mutating genes to give malaria, the scourge of mankind, resistance to modern medicine, what does that say about God? Mark Twain had the answer:
Later he says,
Actually Behe’s use of malaria resistance to quinine is an amazing example of Darwinian evolution via mutation and extreme selection pressure. And of course, sickle cell anemia, which was developed in humans in their “mutation” warfare against malaria.
To heck with the special creation of species, Behe’s big black stripe tagged with “fine tuning” schematizes the special creation of the laws of physics.
I think that’s a hilarious category error. But, I’ve been waiting for years for a creationist myth about cosmology.
Ha! …turtles all the way down…
I always thought Behe was a slow learner, but now I know he’s simply an idiot.
Correction: An idiot with tenure.