Thursday, July 31, 2014

Michael Behe and the edge of evolution

Michael Behe's book, The Edge of Evolution, is very interesting. His main thesis is that there are some genotypes that are beyond the reach of evolution. His examples include genotypes where two or three mutations have to occur simultaneously in order to achieve an effect. The probability to this happening is extremely remote but it could happen in some populations with very large effective population sizes.

The reason why mutations have to happen simultaneously in the same organism, according to Michael Behe, is because any one of them, by itself, is detrimental. This defines the edge of evolution because it's a result that cannot be achieved by mutation and selection (or by drift).

Behe is correct. If a given phenotype absolutely requires that two mutations happen simultaneously then this is going to be almost impossible in most species.

Behe uses the example of drug resistance in Plasmodium falciparum (malaria parasite). Resistance to atovaquone occurs quite often so that's probably due to a single mutation. Resistance to chloroquine, on the other hand, is rare so it's probably due to multiple mutations in the relevant gene (PfCRT, a gene that encodes a transporter protein) [Quinine and Malaria, The Edge of Evolution, Understanding Mutation Rates and Evolution].

Back in 2007 when Behe wrote his book, There was lots and lots of evidence that multiple mutations were required for chloroquine resistance in Plasmodium so none of this was news. The interesting part of his book was the correct claim that there was an edge of evolution and the incorrect claim that you can't get chloroquine resistance by a stepwise, sequential route. He also claimed, incorrectly, that you can't evolve new protein-protein interactions because it requires several simultaneous mutations.

The first "prediction" has been shown to be false. A recent paper by Summers et al. (2014) looks at the common chloroquine resistant strains of the malaria parasite and concludes that, indeed, multiple mutations are required but they accumulated in a stepwise manner. Some of the required mutations were beneficial, some were neutral, and some were detrimental.

Here's the relevant figure (see below) from their paper. Each of the haplotypes (labelled D27, GB4, Ecu1110 etc.) represent a different strain of Plasmodium. The ones that are underlined are the commmon chloroquine resistant strains. There are two families, shown in figure A and figure B.

The authors were able to test the effects of various mutations in order to measure the strength of the transporter protein (chloroquine uptake). They discovered that all chloroquine haplotypes had a K76T mutation (red circle). (This is a lysine to threonine substitution at amino acid 76.) By itself, this was neutral with respect to chloroquine resistance (blue arrows) but in combination with N75E OR N326D (pink circles), the strain acquired a low level of chloroquine resistance (green arrows). Several additional mutations were required in order to confer a significant level of resistance and some of these reduced the level of chloroquine uptake (red arrows).

All of the strains (except D17) are found in naturally occurring Plasmodium populations and the probable pathways to each of the major chloroquine resistant strains are shown. It takes at least four sequential steps with one mutation becoming established in the population before another one occurs.

None of the mutations occurred simultaneously as Behe claimed in his book.

So, how do the IDiots deal with this result, which shows that chlorquine resistant strains can easily evolve without ever coming close to the edge of evolution?

Here's how ... they claim that Michael Behe has been vindicated!!!! [A Pretty Sharp Edge: Reflecting on Michael Behe's Vindication]. The author is Ann Gauger.
I am writing a post that shouldn't have to be written. It's about Dr. Michael Behe's book The Edge of Evolution, what it predicted, how that prediction was confirmed, and how his detractors continue to quibble and obfuscate, claiming that even if he was right he was still somehow wrong. That's not the way scientists are supposed to operate.

In science, theory that explains data and makes a prediction that is experimentally verified is considered to be confirmed. That's the way it is supposed to work. Einstein's general theory of relativity, Mendeleev's periodic table, and many other theories have been verified this way.

Now let's look at Behe's theory. Malaria is a devastating disease caused by the parasite P. falciparum. These parasites are quick to develop resistance to most drugs, but they have had a hard time overcoming chloroquine, requiring more than ten years to develop resistance. In fact, sixty years since the drug's introduction, and after more than 1020 malarial parasites total, resistance to chloroquine has developed fewer than ten times. Why?

In The Edge of Evolution, Behe proposed an answer. His explanation -- his hypothesis, if you will -- is simple. The mutation rate of P. falciparum is roughly 1 in 108 mutations per base pair per parasite. There are on average 1012 parasites in the human body -- that's enough for more than a thousand copies of every possible single mutation to exist somewhere in each infected person. So if resistance required only one mutation, it should have appeared in a few days. However, it took more than a decade for resistance to emerge. Behe argued that therefore at least two mutations must be required for the parasite to develop resistance to chloroquine. Furthermore, those two mutations must each be of no use as single mutations, and those two mutations must be present together in the same organism in order to confer resistance to the drug.

Why did Behe make these predictions? It's a simple calculation, really. If two simultaneous mutations are required for resistance, the rate of that double mutation occurring can be calculated by multiplying the single rates together. That makes the rate for two mutations roughly 1 in 1016 mutations per base pair per parasite. To find those two mutations would require many more trials than are available among the 1012 parasites in each person infected. However, 1020 parasites (the total present in a single year) represent more than enough opportunity for that double mutation to occur.
I sure hope you turned off your irony meter.

Ann Gauger's post is a followup to an exchange that occurred last week when Casey Luskin suggested that Behe's critics should apologize [So, Michael Behe Was Right After All; What Will the Critics Say Now?]. PZ Myers made approximately the same points that I made and he was supported by Ken Miller [Quote-mined by Casey Luskin!] [Falling over the edge].

What we're seeing here (and elsewhere) is a massive failure of the IDiots' ability to deal with inconvenient facts.

UPDATE: Michael Behe, himself, has posted three (count 'em) recent articles on Evolution News & Views (sic). He claims that his ideas on the limits of evolution have been vindicated by confirmation that chloroquine resistance requires more than one mutation. It's important to keep in mind that every single scientist who ever looked at this problem back in 2007, when The Edge of Evolution was published, knew that more than one mutation (and fixation) was required for chloroquine resistance. None of those scientists thought that this was even close to the edge of evolution. They still don't.

A Key Inference of The Edge of Evolution Has Now Been Experimentally Confirmed
It's Tough to Make Predictions, Especially About the Future
The Edge of Evolution: Why Darwin's Mechanism Is Self-Limiting

Summers, R. L., Dave, A., Dolstra, T. J., Bellanca, S., Marchetti, R. V., Nash, M. N., Richards, S. N., Goh, V., Schenk, R. L., Stein, W. D., Kirk, K., Sanchez, C. P., Lanzer, M. and Martin, R. (2014) Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite’s chloroquine resistance transporter. Proceedings of the National Academy of Sciences. published online April 11, 2014. [doi: 10.1073/pnas.1322965111]


  1. Hey, they're catching up now. It won't be long before they'll be updating their calendars to 1985, then...

    "Evolution is not survival of the fittest; it is survival of the adequate," said zoologist Daniel R. Brooks of the University of British Columbia in Vancouver.

  2. Larry: He also claimed, incorrectly, that you can't evolve new protein-protein interactions because it requires several simultaneous mutations.

    I don't think he did claim that.

  3. Before Luskin and Gauger commented on it, Behe wrote three posts on the Summers et al. paper, part III here:

  4. I see Gauger's big problem. This statement...

    "Furthermore, those two mutations must each be of no use as single mutations, and those two mutations must be present together in the same organism in order to confer resistance to the drug."

    ...morphs into this one...

    "If two simultaneous mutations are required for resistance"

    ...and in between the first and the second a new requirement of simultaneity magically appears. (Calling Sidney Harris. Sidney Harris to the ER.) But I see that Gauger makes no mention of the individual mutations being deleterious. Did Behe make that claim?

    Also, none of your exponents are appearing properly on the page, as far as I can see. You have 10^20 as 1020, and so on. I'm assuming this was not Gauger's fault.

    1. Even "those two mutations must each be of no use as single mutations" is not necessary, let alone the leap to "simultaneous" from "present together in the same organism." It could be the case that only one of two mutations was "of no use," or even detrimental. Or there could be more than two mutations in a particular pathway to resistance.

      I wonder whether the religion of these scientists is Xtianity or sloppy reasoning. (That's not necessarily an exclusive "or.")

  5. Bilbo, Behe always said no protein-protein interaction could ever evolve, because protein-protein interactions are irreducibly complex, said he. He was wrong and ID was falsified.

    Behe also claimed that INTRA-molecular interactions were irreducibly complex and could never evolve-- in particular disulfide bridges which have two amino acids (both cysteines), so Behe said disulfide bridges were irreducibly complex and could never evolve. He was wrong and ID was falsified.

    Note, importantly, that Behe's original definition of IC required a system wuth "several parts", but his statements about disulfides mean that "several" = 2 or more, and "parts" can mean amino acids. That makes it easy to falsify ID.

    His ideas were falsified and now the sneaky bastard is trying to redefine Irreducible Complexity AGAIN. He already has many, many permutations of the defintion of IC, enabling him to flip between definitions to evade experimental cases of IC systems that have been observed to evolve. As new experimental info done by real scientists rolls in, Behe just flips to definition #32-J to evade falsification.

    In the post by Behe that Bilbo linked to, Behe slides in definition of IC #37-Q. The new one is:

    "the need to take multiple steps to reach a selected state. "

    Right. That's not what he wrote in 1996. It's not even what he said in 2005 when he was committing perjury on the stand at Dover.

    Anyway, IDiot Behe does not realize that by his new definition of IC, IC has been observed to evolve by natural processes. IDiot Behe does not realize he shot himself in the foot. Again.

    1. Hi Diogenes,

      Citations please.

    2. Diogenes:

      Behe was not accused of committing perjury on the stand in Dover, and having read a good part of the trial transcript, including Behe's testimony, I don't think he did. Rampant stupidity, yes; unreasonableness, yes; gaping holes in logic, yes. Statements he knew to be untrue by his lights, no. One of the defendant school officials was strongly reprimanded by the judge for telling obvious untruths on the witness stand, but was never prosecuted.

      The judge in the trial did say later that the cross-examination of Behe was so devastating to the defendants' case he would like to see it taught in law schools.

    3. Judmarc, I say Behe committed perjury because on the witness stand he lied about what he had written in "Darwin's Black Box." In particular, on the topic of the blood clotting cascade. Recall that the blood clotting cascade can be broadly described has having three segments: intrinsic pathway, extrinsic pathway, and stuff "after the fork." In "DBB" Behe clearly stated that the whole blood clotting cascade, all three segments, were Irreducibly complex. This was immediately falsified when it was pointed out that cetaceans lack some components of the intrinsic pathway. So after that, Behe started claiming that in "DBB" he only said that the pathway "after the fork" was IC, but the intrinsic and extrinsic pathways were not IC. This was how Behe described his book at Dover in 2005. It's completely dishonest.

      The fact that Behe in "Darwin's Black Box" designated both the WHOLE blood clotting cascade, as well as specific proteins he named within the intrinsic pathway, as Irreducibly Complex, is shown by extracts compiled by Nick Matzke here, who also shows Behe contradicting himself in many times and places after Ken Miller et al. pointed out that cetaceans lack some blood clotting factors in the intrinsic pathway. Compare the passages as extracted by Nick Matzke from "Darwin's Black Box" that Behe actually wrote against what Behe said he wrote in "DBB" at his Dover Trial cross-examination. What do you call that discrepancy?

    4. Bilbo,
      tell ya what. If I furnish citations where Behe says that protein-protein binding sites are irreducibly complex, and that protein-protein binding sites have been observed to evolve, will you concede that ID is falsified?

      And ditto for: "disulfide bridges are IC"; "protein-ligand interactions are IC". Will you concede that Intelligent Design can be falsified?

    5. Re judmarc

      Actually, 2 members of the school board, Bonsall and Buckingham, lied through their teeth on the witness stand. At one point during the cross examination of Buckingham, the judge became so enraged at the former's prevarications that he took over the questioning himself.

    6. I really want to repeat my questions to Bilbo, more clearly this time.

      Bilbo already said that he thinks Behe never claimed protein-protein interactions are IC.

      So let's expand on that.

      1. Bilbo, did Michael Behe ever say that disulfide bridges are IC?

      2. Bilbo, did Behe ever say protein-ligand interactions are IC?

      Surely, the Intelligent Design websites will clarify this for you! Won't they? They won't? Oops, you may have to search Panda's Thumb!

    7. colnago: Ah, my loose memory was one of the board members and his father, but I think that's what one of them lied about: the thing where they took up the church collection to buy "Of Pandas and People."

      From the transcript and trial accounts, I would not describe the judge as "enraged," which to me implies hollering, stomping around, etc. It was very obvious, however, that he, as any judge would be, was very disturbed that any witness would think lying in court under oath (i.e., potentially committing a crime in the courtroom itself) was allowable. I think he took over the questioning as much to be extremely sure to let the witnesses know the potential seriousness of what they were doing as anything else.

    8. Diogenes, I've just read through Matske's article and Behe's cross on the blood clotting cascade once again. Weaseling, yes. Not credible, yes. Perjury, no. And certainly the judge also recognized the difference in his treatment of Behe vs. the witnesses who did potentially commit perjury at the trial, and in all of his remarks afterward.

    9. Behe at Dover: The relative importance of the two [clotting initiation] pathways in living organisms is still rather murky... Because of that uncertainty, I said, let's, leaving aside the system before the fork in the pathway, where some details are less well-known, the blood clotting system fits the definition of irreducible complexity.

      This is a pretty good paraphrase of p.86 of the book. Continuing:

      And I noted that the components of the system beyond the fork in the pathway are fibrinogen, prothrombin, Stuart factor, and proaccelerin. So I was focusing on a particular part of the pathway, as I tried to make clear in Darwin's Black Box. If we could go to the next slide. Those components that I was focusing on are down here at the lower parts of the pathway. And I also circled here, for illustration, the extrinsic pathway. It turns out that the pathway can be activated by either one of two directions. And so I concentrated on the parts that were close to the common point after the fork. So if you could, I think, advance one slide. If you concentrate on those components, a number of those components are ones which have been experimentally knocked out such as fibrinogen, prothrombin, and tissue factor. And if we go to the next slide, I have red arrows pointing to those components. And you see that they all fall in the area of the blood clotting cascade that I was specifically restricting my arguments to.... my discussion of irreducible complexity was, I tried to be precise, and... my argument is experimentally supported. [Behe at Dover, 2005]

      Stop right there. He refers to the part after the fork as "the area of the blood clotting cascade that I was specifically restricting my arguments to." That is a lie. In "Darwin's Black Box" he specifically included the stuff before that-- the intrinsic and extrinsic pathways-- as "the system", and as "the irreducibly complex system" which is the same as a "Rube Goldberg machine."

      Behe and Casey Luskin have tried to defend Behe's bait-and-switch by asserting that, when Behe in DBB wrote "the system", he defined "the system" as only the stuff after the fork (not the intrinsic nor extrinsic pathways). That's a lie too, but they want to turn it into a word game where they redefine "the system" and every single word in every sentence they ever wrote. That's why, in the quotes that follow, I'm going to emphasize how Behe defined the term "the system."

      The text of DBB shows Behe using "the system" and "irreducibly complex" and "Rube Goldberg machine" to describe the intrinsic pathway factors often, and sometimes the extrinsic factors also, so "the system" was not restricted to stuff after the fork.

    10. In the passage from DBB below, Behe defines "Rube Goldberg machine" as the same as a single irreducibly complex system, and he includes the intrinsic pathway as part of the irreducibly complex system, calling it "a single system", not divided. I will add notes in brackets [] to clarify which proteins are in which pathways; pay attention to "[Intrinsic]" and "the system".

      Behe, DBB: [T]he Rube Goldberg machine is irreducibly complex. It is a single system composed of several interacting parts... where the removal of any one of the parts causes the system to cease functioning... all system components are required to deliver the blow at the correct time...

      Modern biochemists have discovered a number of Rube Goldberg-like systems... In the biochemical systems the [parts] of the cartoon are replaced by proteins... such as "plasma thromboplastin antecedent" [INTRINSIC] or "high-molecular-weight kininogen [INTRINSIC]."
      [Behe, DBB, p.76-77]

      p. 76-77 of DBB proves that Behe did not restrict his argument to stuff after the fork, contra his Dover testimony when he called the stuff after the fork "the area of the blood clotting cascade that I was specifically restricting my arguments to."
      p. 76-77 also shows that when he said "the system" and "Rube Goldberg machine", he defined "the system", etc. to include the intrinsic and extrinsic pathways, contra what Behe and Luskin would claim post-Dover. Here he includes two more proteins of the intrinsic pathway in his "Rube Goldberg machine" = irreducibly complex system:

      Behe, DBB: "The function of the blood-clotting system is as a... barrier. The components of the system are ordered to that end. Fibrinogen [After Fork], plasminogen, thrombin [After Fork], protein C, Christmas factor [INTRINSIC], and the other components of the pathway together do something that none of the components can do alone. When vitamin K is unavailable or antihemophilic factor [INTRINSIC] is missing, the system crashes just as surely as a Rube Goldberg machine fails if a component is missing." [Michael Behe, DBB, p.204]

    11. Contrast Behe's Dover description of his argument in DBB, above, against the 1996 speech below where Behe describes his book's argument. They're opposites.

      Behe, 1996 speech: "When an animal is cut a protein called Hageman factor [INTRINSIC] sticks to the surface of cells near the wound. Bound Hageman factor is then cleaved by a protein called HMK [INTRINSIC] to yield activated Hageman factor. Immediately the activated Hageman factor converts another protein, called prekallikrein [INTRINSIC], to its active form, kallikrein. Kallikrein helps HMK speed up the conversion of more Hageman factor to its active form. Activated Hageman factor and HMK then together transform another protein, called PTA [INTRINSIC], to its active form. Activated PTA in turn, together with the activated form of another protein (discussed below) called convertin, switch a protein called Christmas factor [INTRINSIC] to its active form. Activated Christmas factor, together with antihemophilic factor [INTRINSIC] (which is itself activated by thrombin [After Fork] in a manner similar to that of proaccelerin [After Fork]) changes Stuart factor [After Fork] to its active form. Stuart factor, working with accelerin, converts prothrombin to thrombin. Finally thrombin cuts fibrinogen [After Fork] to give fibrin, which aggregates with other fibrin molecules to form the meshwork clot...

      Blood clotting requires extreme precision... clotting requires this enormously complex system so that the clot forms only when and only where it is required. Blood clotting is the ultimate Rube Goldberg machine.
      " [Michael J. Behe, “Evidence for Intelligent Design from Biochemistry.” Speech delivered at Discovery Institute’s God & Culture Conference, Discovery Institute, August 10, 1996]

      In this 1996 speech, can you find a distinction of any kind between the intrinsic pathway and the stuff after the fork? There is none; but in his 2005 Dover testimony, he said that in DBB, the stuff after the fork was "the area of the blood clotting cascade that I was specifically restricting my arguments to." Further, in DBB when he said "the system" and "Rube Goldberg machine", he included the intrinsic pathway in "the system" etc.; it was not restricted to stuff after the fork; and from DBB, p.76-77, we saw that Behe equates "Rube Goldberg machine" to "the irreducibly complex system."

    12. So Behe included the intrinsic pathway in his definition of "the system". What about the extrinsic pathway? In 2000, Behe included the extrinsic pathway also:

      Behe, 2000: ...let me first illustrate a well-matched system using the blood-clotting cascade (ref). The active form of one protein of the cascade is called thrombin [After Fork], which cleaves the soluble protein fibrinogen [After Fork] to produce fibrin, the insoluble meshwork of a blood clot… The other proteins of the clotting cascade (Stuart factor [After Fork], proaccelerin [After Fork], tissue factor [EXTRINSIC], and so on) have similar powers of discrimination. So do virtually all of the components of the molecular machines I discussed in Darwin's Black Box...

      Yet contrast this case [redundant systems] with that of mice in which the gene for either fibrinogen [After Fork] (ref), tissue factor [EXTRINSIC] (ref), or prothrombin [After Fork] (ref) has been knocked out. Those proteins are all components of the blood clotting cascade, which I discussed prominently in
      Darwin’s Black Box (1996, Ch. 4), claiming it is irreducibly complex. [Michael Behe, Self-Organization and Irreducibly Complex Systems: A Reply to Shanks and Joplin, Philosophy of Science 67 (March 2000)]

      A direct contradiction. At Dover, he called the stuff after the fork "the area of the blood clotting cascade that I was specifically restricting my arguments to" when he wrote DBB. But in 2000, he described the EXTRINSIC pathway tissue factor as part of "all components of the blood clotting cascade, which I discussed prominently in Darwin’s Black Box... claiming it is irreducibly complex". Which is it-- "Discussed prominently" or "restricted" out? Which is the lie?

      In DBB, when Behe said "the system" and "Rube Goldberg machine", which he equated to "irreducibly complex system", he included both intrinsic and extrinsic pathways:

      Behe, DBB: "Since each step necessarily requires several parts, not only is the entire blood-clotting system irreducibly complex, but so is each step in the pathway... each of the control points of the blood-clotting cascade needs both an inactive proenzyme and a separate enzyme to activate it...

      The formation, limitation, strengthening, and removal of a blood clot is an integrated biological system, and problems with single components can cause the system to fail... The most common form of hemophilia arises from a deficiency of antihemophilic factor [INTRINSIC], which helps activated Christmas factor [INTRINSIC] in the conversion of Stuart factor [After Fork] to its active form. Lack of Christmas factor is the second most common form of hemophilia... Bleeding disorders also accompany deficiencies in FSF [EXTRINSIC], vitamin K, or 012-antiplasmin, which are not involved directly in clotting...

      Is it possible that this ultra-complex system could have evolved according to Darwinian theory?"
      [Michael Behe, DBB, p.87-88]

    13. Now let's see more of Behe lying at Dover:

      Q. ...It [DBB] says, The components of the system beyond the fork in the pathway are fibrinogen, prothrombin, Stuart factor, and proaccelerin [stuff After the Fork]. That's your irreducibly complex system, isn't it, Professor Behe?

      A. No, it's not. Again, I was confining my discussion to the point after the fork in the pathway because, as I said in the book, much more is known about that...

      He did no such thing; he did not confine his discussion to the point after the fork, as the passages above prove. Continuing with Behe:

      Q. So you have to have those four [proteins after the fork], right?

      A. Yes, those four are needed for the system to work. But -- and I confined my discussion to them.

      [Behe at Dover]

      Ha! In DBB he did not confine his discussion to the mere four proteins after the fork, as the passages above proved; and in fact, in DBB he explicitly stated he would discuss 20 proteins, "a score", not just the four after the fork, and all 20 were "the system":

      Behe, DBB: "Biochemical investigation... has shown that blood clotting is a very complex, intricately woven system consisting of a score of interdependent protein parts. The absence of, or significant defects in, any one of a number of the components causes the system to fail...

      Over the next few pages you will meet the score of protein players in the game of blood clotting and learn a bit about their roles."
      [Michael Behe, DBB, p.78-9]

      But at Dover he said "I was confining my discussion to the point after the fork" and "I confined my discussion" to just those four proteins! But in the book, he said 20. Which was it, 4 or 20? Who cares, it looks like perjury to me.

    14. Hi Diogenes,

      Let me quote Behe from DBB:

      Leaving aside the system before the fork in the pathway, where some details are less well known, the blood-clotting system fits the definition of irreducible complexity. That is, it is a single system composed of several interacting parts that contribute to the basic function, and where the removal of any one of the parts causes the system effectively to cease functioning. The function of the blood clotting system is to form a solid barrier at the right time and place that is able to stop blood flow out of an injured vessel. The components of the system (beyond the fork in the pathway) are fibrinogen, prothrombin, Stuart factor, and proaccelerin. (p. 86)

      That makes it pretty clear exactly which part of the larger blood clotting cascade he is referring to when he says that is is irreducibly complex.

      Meanwhile, no, I will not say ID is falsified if Behe made some rash statements. However, just as you have taken Behe's statements out of context in order to try to show that he committed perjury, I'm rather confident that the other claims you have made about what Behe considers IC or what is needed in order to evolve a protein binding site are also taken out of context.

      Ever since you failed to reply Mike Gene at his website after he answered you, it is clear that you are not an internet debater who is to be trusted or taken seriously.

    15. I will not say ID is falsified if Behe made some rash statements.

      What about if he didn't just make some rash statements, but if he, as the only ID author who's tried to get into any sort of detail about biochemical systems and evolution, was so spectacularly ridiculously awful in trying to defend what he wrote that his cross examination has been cited as something that should be taught in law schools?

      Just because neither I nor the judge thought Behe's testimony amounted to perjury doesn't mean his utterly flustered tap-dancing when given the chance to explain himself in court has any chance of being correct.

    16. ID does not make testable claims, so it is not correct to say that ID has been falsified. ID is entirely a criticism of evolution (IDiots don't understand the distinction) and this study has simply demolished another of their BS arguments against evolution.

  6. These comments by the IDiots are truly bizarre. Here's an excerpt from Luskin's article linked above:

    As Dr. Behe explained, this was a major point of contention among critics of his book. They claimed that Behe mistakenly thought chloroquine resistance required multiple simultaneous mutations, when in actuality it could arise through sequential mutations, each conferring a successively greater resistance-advantage. It can no longer be denied that the critics were dead wrong: chloroquine resistance does not arise at all until two mutations or more are present.

    There's always an ongoing question of whether the ID creationists are so stupid that they believe the things they write, or so dishonest that they hope their readership won't notice their blatant errors. Passages like the above make it hard for me to dismiss the second option. The bait and switch here is twofold: Firstly, as far as I can recall, Behe never explicitly said that chloroquine resistance required two simultaneous mutations. His error was more profound than this: He said the mutations could have occurred sequentially but the probabilites he calculated were based on the odds of them occurring simultaneously. This is a basic error in high-school level math, as explained here:

    Luskin's disingenuousness does not end there. Note how he ascribes to Behe's critics the claim that the sequential mutations must each add an incremental advantage in order to be retained in the population. As Larry points out above, of course, these mutations could also be neutral or even deleterious. I wonder if Luskin realizes he is finally endorsing Nearly Neutral Theory, which Larry has been trying to explain to him for years.

    There's an even more puzzling issue here. Behe writes:

    Here's something to ponder long and hard: Malaria was intentionally designed. The molecular machinery with which the parasite invades red blood cells is an exquisitely purposeful arrangement of parts. C-Eve's children died in her arms partly because an intelligent agent deliberately made malaria, or at least something very similar to it.

    What sort of designer is that? What sort of 'fine-tuning' leads to untold human misery? To countless mothers mourning countless children? Did a hateful, malign being make intelligent life in order to torture it? One who relishes cries of pain?

    It seems to me that Summers' paper clearly refutes the claim that malaria was "designed", since chloroguine resistance evolved right under the investigators' eyes. So what exactly is Behe, Luskin and Gauger saying? That the first mutation (which Gauger presumes made the parasite "sickly") was sustained by miraculous means until the second mutation could arise to created chloroquine resistance? Are they, in fact, claiming the Summers et al have directly witnessed the hand of God at work? That seems to be the inevitable conclusion to draw from their claims, yet they seem remarkably coy about proclaiming this momentuous event. Why could that be?

    1. I realize now I misrepresented the Summers study, in that it did not involve directly observing the evolution of chloroquine resistance. My main points still stand, however.

    2. Edge of Evolution, pg 237. (I admit, I don't have the book myself, but that quotation has been given on so many sources, I am confident it is accurate.)

    3. Can someone who has access to the book elaborate? I'm fairly sure that Behe wouldn't leave us with the conclusion that god is evil. So how does he answer his own questions?

  7. Hi Larry,

    Now that I think about it, the fact that P. falciparum only needed two sequential mutations and still had difficulty developing chloroquine resistance, despite an incredibly huge population size, weakens your case and strengthens Behe's.

    Meanwhile, why don't you take
    the Behe challenge?

    1. How in the world does it strengthen Behe's case? In order for Plasmodium falciparum to develop significant chloroquine resistance a minimum of FOUR mutations were necessary and they had to be brought together in the same gene.The frequencies of each of the alleles, or combinations of alleles, had to rise to appreciable levels in some subpopulation of the parasite. Many of them were lost on the way.

      All this had to happen while the populations were reproducing in the absence of chloroquine most of the time.

      All this tells us is that some evolutionary pathways are difficult and improbable but we've known that for a century. On the other hand, we've only known about Neutral Theory for half a century. The remarkable thing about recent posts by IDiots is that they are still half a century behind in evolutionary biology.

    2. Meanwhile, why don't you take the Behe challenge?

      Because there are too many unknowns and because Behe is making too many stupid assumptions. I agree with Behe that chloroquine resistance is a rare event but I don't know how to calculate an exact probability based on the results of the Summers et al. paper.

    3. Read the paper instead of listening to Behe.
      Two mutations only confers a low level of resistance. So if chloroquine dosage is high, cells having only two mutations in PfCRT may not survive. There are other pitfalls too. For instance, if K76 gets mutated to any amino acid other than T, the ability to transport chloroquine weakens further. Additionally, the mutations also have to occur in a specific order.

      Moreover, the paper states that some combination of mutations increases fitness under chloroquine but decreases fitness when chloroquine is absent. Such cells will be outcompeted by their wild-type relatives when chloroquine is withdrawn.

      Given all these factors, it's hardly surprising that Plasmodium has a hard time developing resistance against chloroquine.

    4. Bilbo: "Meanwhile, why don't you take the Behe challenge?"

      Besides his other problems, I'll add on that Behe is, at best, demanding that we compute a probability density. But in classical statistics, no hypothesis can be tested or refuted by computing a a probability density no matter how small; only a computation of a probability mass can test a hypothesis.

      Here's the difference: you may have heard of the "Bridge Hand Fallacy." You win a game of bridge, then you compute the probability density of getting the specific combinations of cards that you used to win the game, by assuming a process of random shuffling and selection. This probability will undoubtedly be very tiny but who cares, it can't test the hypothesis that "God made me win the game of bridge" because it's a probability density and that can't test a hypothesis.

      To compute a probability mass you would have to

      1. First you have to define your hypothesis well, e.g. "The cards with which I won the game must have been chosen by a non-stochastic process",

      2. Then compile a list of all possible card hands by which you could have won the game, even though you never saw most of those conceivable hands (this step is called defining a rejection region.)

      3. Then you compute a probability density for each hand of cards by assuming a specific process, e.g. totally stochastic shuffling and selection.

      4. The you sum the probability density from step 3 over all conceivable winning hands from step 2. The integral is called the probability mass. This and this only can test or refute your hypothesis.

      The "Bridge Hand fallacy" consists of using a probability density instead of a probability mass to test a hypothesis. This is how IDcreationists tell church audiences that science is done. IDcreationists like Behe just make religious people dumber and dumber.

      Now Bilbo, I've a question for you.

      Do you think Behe ever attempted steps 1, 2, 3 and 4 above? Do you think he got past steps 1 and 2?

      In what you call "the Behe challenge", did Behe define his hypothesis (beyond "God did it by magic") and define his rejection regions? If so, what is his rejection region? Please tell us Behe's rejection region.

      No? Do you want us to be dummies and compute probability densities and call them probability mass?

    5. That would be an interesting twist, but where's the evidence?

    6. Very unlikely, Bilbo's been around a long time and doesn't act much like Luskin.

  8. Still, it's nice to know that the Designer still pops up from time to time to circumvent the 'edge' and actually confer that which evolution cannot achieve, and screw with our defences against disease. What a guy! Still not over that unpleasantness with the apple.

    1. Makes you wonder what the hell the Dear Leader, ehh sorry, "designer" is really up to with all this crap. Giving us immune systems to fight off a whole host of common parasites and pathogens(some of which are critically dependent on us and can't live anywhere else), why not simply make them incapable of infecting us in the first place? What's the deal with a gut bacterial flora anyway? It can leak out and enter the bloodstream and make us extremely sick. Why not just give the cells in our gut all the tools and remedies to properly digest what we eat?

      And then even worse when this entity decides some of these pathogens just aren't lethal enough and it makes ebola and similar sick shit.

    2. I see considerable support for the multiple designer theory. And clearly, some of the designers don't much like the other designers.

  9. Say, isn't that photo of Gauger the one in which she has been green-screened into a lab? Not relevant to this discussion, but telling nevertheless.

  10. Lawrence A. Moran: Why do you call them IDiots? Is there a mean word that they call you?

    1. Yes, they use lots of insulting words and phrases to refer to real scientists who disagree with them.

      I use the word "IDiots" to do double duty. First, it identifies those who believe in Intelligent Design Creationism as opposed to other forms of creationism. Second, it highlights the fact that they are pretty stupid about evolution.

    2. lmdp is apparently blissfully ignorant of the pro-ID propaganda film Expelled: No Intelligence Allowed, the entire point of which was to smear real scientists as Nazi-like censors who brutally suppress any challenge to the dogma they unquestioningly accept. As well, lmdp is apparently ignorant of all the instances of ID-pushers comparing real scientists to Communists and Nazis and other such no-goodniks (some of those instances are documented here).
      At least, I would hope lmdp is blissfully ignorant of those things. Because if lmdp actually was aware of those things when they asked "Is there a mean word [ID-pushers] call [Prof. Moran]?", that would not reflect well on lmdp's intellectual capacities.

  11. Does it make you angry that they don't understand evolution?

    1. Yes. It makes me angry that they pretend to understand evolution and lie to their followers.

    2. Why get angry? People are lied to all the time. What would you say is at stake?

    3. Truth, honesty, and rationality are at stake. I think those are values worth fighting for. Don't you? Or would you prefer to live in a society where it's socially acceptable to lie about scientific facts?

    4. sez ldmp: "What would you say is at stake?"
      Read the Wedge Document. If, after reading the Wedge, you still wonder what might be at stake, do feel free to inquire again.

    5. Hey lmdp (On Blogger since January 2015, indeed a freshly minted drive by troll identity), does it make you angry when people use mean words ? People use mean words all the time. What would you say is at stake ?

      Explain why not getting angry and using mean words is more important, at least to the extent that you were motivated to comment here, than adherence to a rational, evidence based reality.

    6. Getting angry and calling names because someone doesn't believe what I know to be true doesn't seem very rational to me. I am not emotionally invested in either side, this topic is very interesting to me. Just hoping to get a little insight. This is my first time commenting on a blog. This will be my last comment. Thank you

    7. As humans, we live by a lot of moral principles, but within science, there is just one principle that we must all agree on; honesty. We can only do science well based on honest reports of what has been seen and what logically follows from that. So, the first moral principle of science is honesty.

      Much anti-evolution thought and writing is based on ignorance, which makes me sad. However, some is based on dishonesty. Dishonestly repeating things after receiving careful explanations about why they are false. Dishonestly quote-mining. Dishonestly contorting logic to excuse evidence that can't be denied. Dishonestly playing with words to define evolution away. This is deeply wrong. This is the antithesis of doing science well. This dishonesty is well worth being angry about.

      Enough people who are being dishonest about evolution try to pretend they're just ignorant that we may occasionally be angry with people who are not actually lying (merely wrong). This is, I think, unfortunate, but it certainly wastes a lot less time than trying to answer troll questions.

    8. Ah, flouncing while clutching at pearls. Good day, sir. I said "good day"!