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Ken Miller, the honest Darwinist

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Ken Miller just published a review of Michael Behe’s book, Edge of Evolution. Here is Miller at his best:

but Behe has built his entire thesis on this error. Telling his readers that the production of so much as a single new protein-to-protein binding site is “beyond the edge of evolution”, he proclaims darwinian evolution to be a hopeless failure. Apparently he has not followed recent studies exploring the evolution of hormone-receptor complexes by sequential mutations (Science 312, 97–101; 2006),

Ken Miller
Falling over the edge

Miller falsely accuses Behe of not following the Science (2006) paper, yet it’s hard to imagine that Miller missed the widely available public response by Behe of that very study. How could Miller accuse Behe of not following the study, when Behe said:

The study by Bridgham et al (2006) published in the April 7 issue of Science is the lamest attempt yet — and perhaps the lamest attempt that’s even possible — to deflect the problem that irreducible complexity poses for Darwinism
….

The fact that such very modest results are ballyhooed owes more, I strongly suspect, to the antipathy that many scientists feel toward ID than to the intrinsic value of the experiment itself.

In conclusion, the results (and even the imagined-but-problematic scenario) are well within what an ID proponent already would think Darwinian processes could do, so they won’t affect our evaluation of the science. But it’s nice to know that Science magazine is thinking about us!

Michael Behe
The Lamest Attempt Yet to Answer the Challenge Irreducible Complexity,

Despite Behe’s public and widely available commentary on this study, Miller falsely accuses Behe of not following it. Miller asserts boldly, “Apparently he [Behe] has not followed recent studies exploring the evolution of hormone-receptor complexes by sequential mutations (Science 312, 97–101; 2006)“.

I get it, Miller didn’t realize Behe has indeed followed this study and that Behe has even publicly commented on the Discovery Institute’s website. Miller couldn’t possibly have been so dastardly as to actually know Behe published responses to the study, and then falsely accuse Behe of not following the study.

Miller couldn’t possibly be that dastardly. We can therefore attribute it to Miller’s ignorance and simply presume, even though Miller has been obsessed by ID activities, he missed Behe response on the DI website. That can only be the explanation since Miller, being the honest Darwinist he is, can’t possibly do such a dastardly thing. We must chalk this up to his honest ignorance.

[UPDATE:

I found more examples of Ken’s Honesty:

1. Miller falsely insinuates Behe waves away “evidence”

2. Miller’s case against a non-220 CQRs self-destructs by the very paper he cites against Behe

3. Ken Miller needs to know 2004 does not equal 2005

4. Ken Miller reapeats the same misrepresentation he made under oath in Dover

]

Notes:

1. Ken Miller is the guy who has taken various bruisings from scientific evidence and continues his misrepresentations and story telling as he did under oath in the Dover trial. [See: Ken Miller may face more embarrassing facts, Behe’s DBB vindicated and Ken Miller caught making factually incorrect statements under oath]

2. Miller has not (to my knowledge) retracted yet another misrepresentation he made of Behe some time back.

Mike Gene observes in 9+2 = Straw:

In his book, Finding Darwin’s God, Miller finds himself “amused” at Behe’s argument regarding the eukaryotic flagellum, adding, “A phone call to any biologist who had ever actually studied cilia and flagella would have told Behe that he’s wrong in his contention that the 9+2 structure is the only way to make a working cilium or flagellum.” (p.141).
….
But I can’t find where Behe ever raised this contention.
….
what is annoying is that Miller uses this misrepresentation as part of a carefully crafted ad hominem. He begins with “amusement” that leads up to his “A phone call to any biologist” schtick.

Mike Gene

Comments
I don’t see how we extrapolate from CQR to limits. May I suggest you read the book and see if that helps your understanding? That's the purpose of the book, after all.DaveScot
July 4, 2007
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A quick reply before firing up the barby ... I don't think anyone is claiming that CQR is a huge evolutionary leap. Also, if the 10^20 figure isn't really correct, then I'm having a hard time seeing how CQR actually relates to, let alone helps define, the "Edge of Evolution". It's just one more example of a multi-genic trait that falls on this side of the "Edge of Evolution". I don't see how we extrapolate from CQR to limits.Art2
July 4, 2007
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Art2, Thank you for that consideration. Let me add however, the bottom line is that CQR does not appear to be a particularly sophisticated evolutionary change. It would be hard to argue that this shows the power of Darwinian evolution to create large scale complexity. It seems to show there are limits. Salvadorscordova
July 4, 2007
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Hi magnan, In tossing the number 10^20 out, White seems to be referring to the occurrence of, not a simultaneous double mutation in PfCRT, but rather the coincidence, in a surviving parasite, of resistance-related alleles in three different genes. One allele seems to require two mutations, but it is not clear how many mutations "make up" the other resistance alleles. So, in terms of estimating the "Edge of Evolution", this number (10^20) would seem to be pretty arbitrary, and certainly not related in any strict quantitative way to the simultaneous occurrence of two point mutations. This may be why we can point to examples of at least three "CCC"s occurring, simultaneously and by random processes, at least 30 orders of magnitude more frequently than predicted by Behe's estimates. I think we need to be very tentative about this number.Art2
July 4, 2007
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Art2: "Magnan, I think the three sentences immediately preceding the first quote you give from White’s review are pretty important. And I think they change matters greatly." Please explain.magnan
July 4, 2007
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The objection has been made that the clinically derived probabilities of 10^20 and 10^12 from scientific studies are not spontaneous mutation rates, but really reflect probabilities of CQR after periodically varying selection due to body environmental attack and transition outside the body to the mosquito life cycle. This objection does not affect Behe's conclusion that a slightly more elaborate combination of two primary required specific mutations has only one hundred millionth the chance of spontaneously occurring in a single plasmodium than a single mutation. This is because Behe's estimate is based on the difference between the two numbers, and both numbers have the same bias. The implications of this reasoning for NDE are untouched. This objection, even if correct relative to the meaning of the probability numbers, is also irrelevant to Behe's primary thesis. He shows that there is a vanishingly small likelihood of even a relatively simple combination of specific mutations (as for CQ resistance) occurring in the human population over even millions of years. Say P. falciparum actually has a spontaneous mutation rate for CQR one billion (10^9) times the 10^20 figure in White's paper. This would be 1 in 10^(20-9) = 1 in 10^11 multiplications. Behe does his extrapolation of the CQR estimates to human evolution on page 60 of TEOE. He concludes by simple calculation that "The ratio of humanoid creatures in the last 10 million years to the number of parasites needed for chloroquine resistance is one to a hundred million." This is 1 over 10^8. Even if the number of parasites needed is actually 10^11 not 10^20, then his estimate becomes (one in 10^8) times 10^9 = 10^-1. Still only 1 in 10 for just a relatively simple change of a few substitutions, in 10 million years. Pretty poor performance for NDE. The random mutations or other genetic changes required to build Homo Sapiens from a primitive prehominid would be vastly, astronomically greater than a few single point mutations, so this makes human evolution by a NDE process ridiculous. For the same reasons, quibbling over whether two or three mutations are required for CQR, or whether they need to be simultaneous or sequential, is also irrelevant to Behe's argument. On top of this, Behe didn't even bother to point out that his extrapolated estimate is based on the P. falciparum genome size of about one hundred million, much less than that of humans. The human genome is about 3 billion nucleotides, making the probability of specific mutational changes by random mutation much less.magnan
July 4, 2007
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Sal I don't think I know how to answer it.dougcampo
July 3, 2007
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I see JAM has avoided answering my question, dougcampo as well.scordova
July 3, 2007
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Magnan, I think the three sentences immediately preceding the first quote you give from White's review are pretty important. And I think they change matters greatly.Art2
July 2, 2007
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While I'm on my Berlinski kick. You guys and gals who haven't read this article might enjoy it. http://www.discovery.org/scripts/viewDB/index.php?command=view&id=2450dougcampo
July 2, 2007
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Here's the quote again from White's paper: "Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications. " Wikipedia definition of "de novo" for evolutionary biology: "De novo mutation: a genetic mutation that neither parent possessed nor transmitted. " So White in the paper cited by Behe clearly states that the estimate of one in 10^20 multiplications is for a new occurrence at random in one parasite in one multiplication, period. Not per parasite for just populations where a parasite with spontaneous CQR won out in a selection process within a human body. Not per parasite for populations resulting from transmission of CQR Plasmodia to a human by a mosquito following continually reversed selection between human infection phases and mosquito life cycles. However, he did enumerate several selection factors that work to slow CQR becoming established in a population in a human body, and becoming transmissible. So in coming up with the 10^20 estimate using in part clinical data White must have accounted for these factors. If he didn't, he would have been guilty of the same mistake Behe is being accused of. Concerning the rapidly reversing fitness landscape argument. White says the fitness factor of the CQR strain is 75%-85% that of the wild type. This is weak selection compared to the very strong selection for CQ resistance in a multiplying population in a sick human. In addition, the population in a human victim is vastly greater than in the mosquitoes. So during an outbreak RM (and other sources of random variation) + NS in infected humans can be expected to vastly predominate over any reverse selection during the mosquito reproductive life cycle. So an alternating fitness landscape doesn't explain the rarity of CQR. Anyway, this "constantly changing fitness landscape" idea is predominantly used by Darwinists to explain why organisms aren't really trapped on local maxima or peaks. Here it is being used to explain an organism being trapped for a long time on a peak. It looks like the dynamically changing fitness landscape argument is going to be an all-purpose "explain away" tool to defeat any and all attacks on NDE. Of course studiously ignoring that it loses all credibility, as if it had any in the first place. A time varying fitness landscape still doesn't get around the probablistic difficulty of credibly assuming that a random walk can move from one isolated "peak" to another. This is just another rhetorical ploy. This debate needs to be kept in perspective. This criticism certainly doesn't challenge any of the many other factors cited by ID advocates. For instance, the No Free Lunch mathematical arguments against NDE including time varying "fitness landscape" explanations, or the general lack of intermediates predicted by NDE, the Cambrian Explosion, Haldane's dilemma, genetic entropy, irreducibly complex biological systems, etc. etc. It doesn't affect Behe's point that mutation (including all sources of random variation including recombination) has to work with pre-existing cellular machinery, so there is a very limited number of things it can do, to paraphrase TEOE page 77. This is another aspect or way of looking at these limitations and is overwhelmingly confirmed by evidence, including the Plasmodium example. At its best this criticises Behe's particular malaria Plasmodium example of the limits of Darwinian evolution. He chose this because of its huge population numbers. It doesn't affect his other examples of such limits, for instance the bacterial culture studies with E. coli that generated nothing fundamentally new, mainly devolution. It certainly doesn't show an actual example of a complicated biological innovation arising by NDE processes. Surely the evolutionary biologists should be able to find an example of this in historical time with at least some single celled organism with huge populations and short generation times and strong new selective pressures due to human activities. Until then it's back to the "just so" stories again.magnan
July 2, 2007
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"When I called you on your pitiful lies you changed your story" Darwinists are going to say anything and everything in an attempt to scuttle ID.dougcampo
July 2, 2007
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JAM
The specific substitutions don’t matter for his calculation. The problem is that he claims that two are required, and that they have to occur simultaneously. It’s an exponential error. Behe claims that two amino acid residues must be changed in a single mutational event. There is no evidence to support his claim.
Go back and read your comment at #25. Your whole point was that Behe was proven wrong because some strains of CQR malaria plasmodium do not have a mutation at the 220 position. Now suddenly the problem is Behe wants two simultaneous mutations and the specific substitutions don’t matter? You claimed to give two cites where Behe said CQR required mutations at 76 and 220. The quotes clearly say no such thing so now you are changing your argument! Oh, by the way, your new argument is just as much BS as your previous one. Behe never claims the mutations must be in a single mutational event! What Behe requires is two mutations before CQR emerges, or at least CQR with a selective advantage. If CQR occurs after one mutation, say at 76, it doesn’t confer a significant selective advantage. Compare to atovaquone where in a clinical trial one in three people had a recrudescence of infection. Resistance to atovaquone is known to arise after a single mutation to the cytochrome b gene.
I’d like you to answer this question: why, given the availability of primary human cell cultures, did Behe choose to extrapolate from an organism whose mutation rate is impossible to directly measure, and which is very distantly related to us?
For one thing Behe isn’t studying human evolution, he is studying all of evolution. Behe is looking at malaria because of the large population sizes and the decades of observation.
White uses the verbs “developing” and “arising,” not “mutating” to describe what happens in populations. White uses the term “mutation rates” to describe what is measured more directly. White also uses “apparent” to explain that the rate Behe is peddling as reflecting the mutation rate is not real, and explains additional reasons why CQR alleles will have trouble becoming established in a population:
Wrong again. Here is what White says, “ This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications ." Notice JAM that is “per-parasite probability.” White distinguishes between “developing resistance” and the “de novo selection of resistance.” The calculation of the per parasite probability of developing resistance 10^20 is based only on the population of malaria in people who are sick, where probability of selection of de novo resistance is very high. As White states, “Taken together, the balance of evidence strongly favors acute symptomatic infection as the source of de novo antimalarial resistance.” Gametocytes carrying the resistance genes reach transmissible densities when the resistant biomass has expanded to a population size close to that necessary to produce illness (>107 parasites). Furthermore the relative fitness of CQR strains is .76 or .85, so it is not immediately deselected for lack of fitness in an environment without selective pressure for CQR. At any rate, Behe offers 10^20 as a rough estimate only so your is completely de minimas. You started off accusing Behe of claiming that CQR always required mutations at 76 and 220. When it was pointed out that Behe said “almost always” you claimed Behe contradicted himself. When Sal asked you to produce a quote where Behe contradicted himself you dishonestly cited pages that said nothing of the sort. When I called you on your pitiful lies you changed your storyJehu
July 2, 2007
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Discovery Institute to fund...maybe a few million a year?
I wish that could be the case...
Discovery Institute’s Center for Science and Culture (its program on intelligent design and evolution) only spent $1.2 million in 2003, the year that Olson uses for his film. In 2004 it spent the same, and in 2005 it spent $1.6 million. Indeed, the budget for the entire Discovery Institute, including expenditures on non-intelligent design programs on transportation, technology, and other topics, has never reached $5 million. In 2003, the Institute as a whole spent $2.5 million, or half the figure cited by Olson. In 2004, it spent $3.5 million, and in 2005 it spent $3.9 million. These facts are publicly available for anyone to check on the Institute’s Form 990s posted at www.guidestar.com.
Patrick
July 2, 2007
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This a great quote from David Berlinski that I want to share with you guys. ------------------------------------ The ID movement in its attack on Darwinism has simply articulated what many people instinctively feel. Darwin’s theory is plain nuts. It is not supported by the evidence; it has no organizing principles; it is incoherent on its face; it flies against all common experience, and it is poisonous in its implications. And another thing. It is easy to understand. Anyone can become an evolutionary biologist in an afternoon. Just read a book. Most of them are half illustrations anyway. It’s not like studying mathematics or physics, lot of head splitting stuff there.dougcampo
July 2, 2007
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'I imagine they could fund a lab, a few researchers and a few graduate students for the several years the work would take out of their budget' This is a good idea Patrick.dougcampo
July 2, 2007
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Jerry, I was not feigning concern for ID. Actually, if you thought that then obviously I failed to successfully get across what I was trying to say.dougcampo
July 2, 2007
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In light of the above illustration, note how readily JAM will be willing to answer the question I posed to him. He obfuscated when I posed the question to him earlier. He's invited to answer my rephrased question.scordova
July 2, 2007
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Let me suggest to the reader that some of the reading of Behe by the critics is uncharitable and highly disingenuous. To illustrate my point, let's say I had a math book and read on one page: f(x) = 2 and then on another page f(x) = x + 7 Would I go around arguing the author contradicted himself, or that the author is mistaken to say f(x) = 2, when he later says f(x) = x + 7? Of course not! However, the critics are pulling a similar stunt, and being very disingenuous by pulling Behe's 2 mutation quotes and computations out of context. JAM said Behe had a false claim on page 59, but what is the context. The context begins on page 57:
Suppose that P. falciparum need several separate mutations just to deal with one antimalarial drug. Suppose that changing one amino acid wasn't enough. Suppose that two different amino acids had to be changed before a beneficial effect for the parasite showed up. In that case...
Behe is creating an illustration to help us understand later discussions. Let me point the reader to how Michael Lynch pulled a similar unwholsome trick. See: Becoming a Jedi Master in the online ID Wars I gave the following illustration. ===== consider the following hypothetical example where Joe Proponent tries to advance a new theory in the field of medicine,
Joe Proponent writes: The research in our paper will focus on males who weigh 200 pounds and up…given that the focus of our research is on males who 200 pounds and up, males weighing 200 pounds and up will be the starting assumption in our model…there are other areas of research that can be pursued, namely males weighing less than 200 pounds, but that was not the focus of our research…..
and then StrawMan Critic comes along and tries to discredit Joe Proponent’s work, StrawMan Critic responds:
It is an unwarranted assumption that males weigh 200 pounds and up, we have numerous examples where this isn’t true. This is gross mischaracterization of the well established scientific literature. Here is a daunting list of peer-reviewed papers demonstrating that their assumptions that males weigh 200 pounds or more is totally unwarranted…therefore their model is false…therefore the conclusions of the research should be categorically rejected.
I hope the reader sees the flaws in StrawMan Crtitic’s argument. In the ID wars, such StrawMan arguments are very subtle, couched in technical language, and window dressed with citations to peer-reviewed literature. The screeds by the critics follow the same unwholose rhetorical form. The misrepresentation of the 2 mutation assumption is being promoted by the anti-ID critics in the same manner.scordova
July 2, 2007
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dougcampo, Patrick Caldon provied no refutal of ID and neither has JAM. Patrick Caldon provided one interesting mutation in a dog and a couple mentions to some others and JAM is desperately trying to find some minutae wrong with Behe's book. If anything, the triviality of their replies is indicative that the basic premise of ID is even stronger. So I do not understand your feigned concern for the ID movement when as we often say, "Is this all they can come up with."jerry
July 2, 2007
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dougcampo, You can answer the question I posed to JAM. If you choose not to, I consider your empty boast just that, an empty boast. If you don't answer, consider yourself univited to this thread as well. Salscordova
July 2, 2007
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JAM: I was away for a bit, otherwise I would have weighed in earlier:
I asked you: Simultaneoulsy for what? Simultaneously for any CQR to exist at all or just for that particular form of resistance?
I asked a simple question, and you obfuscated and didn't answer. The particular form of restance in question was the 76 and 220 resistance. You started obfuscating about dosage levels of CQ. That was just obfuscation. If a malarial strain has a 76 and 220 form of resitance in place, then it has a 76 and 220 form of resitance. So let me try to rephrase the question. Did Behe argue that a malarial strain will have CQ resistance if and only if it has the 76 and 220 mutations that confer resistance? You have 3 options: 1. yes 2. no 3. JAM doesn't know how to answer If you answer #3, then explain why you don't know how to answer. Answer, or consider yourself univited to this thread.scordova
July 2, 2007
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dougcampo, Speaking as someone who's more theistic evolutionist than IDist, I don't think - even if Behe's claims turn out to be incorrect - the ID movement is in trouble. No more than evolution was in real trouble when Gould and Dawkins squared off, or the usefulness of junk DNA was (and is) pointed out. If a claim is proven to be wrong, the claim is either amended as needed, or discarded. That's science. At worst for ID is the realization that finding a way to detect design in biological processes (for example) is not available. In which case the argument places a foot more firmly in the realm of the philosophical rather than the scientific. Still, I think the ID movement has already succeeded in doing one thing - getting people to look at science with fresh eyes and attitudes, rather than the ones the high priests of science demand they rely on.nullasalus
July 2, 2007
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dougcampo, I'd hardly describe my mutterings as overwhelming opposition, but I agree that it does seem a great shame that Michael Behe did not take the opportunity to do some experiments and properly characterize the development of CQR in its myriad forms. Numbers of people have done in-vitro work on this, the protocols seem reasonably well understood, what's needed now is a lot of grunt work to actually nail down what the probabilities of various sequences of mutation are. If it happened to contribute something to the ID debate, all for the good, but a precise description of the probabilities of CQR would almost certainly be invaluable in the construction of anti-malarial strategies, and could quite possibly save many hundreds of thousands of lives. This would surely be an excellent piece of work for the Discovery Institute to fund, I imagine they could fund a lab, a few researchers and a few graduate students for the several years the work would take out of their budget, maybe a few million a year? And if indeed the evidence (in this particular regard) did not end up showing the truth of ID, at least they would have the consolation that they had benefited the lot of humanity.Patrick Caldon
July 1, 2007
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If ID people don't find something to discredit Darwinism soon you are going to lose the American people. I'm sorry, I want to believe and I really support everything you guys are doing but you are against what seems like overwhelming opposition. Both from the Darwinists and a culture that just doesn't care anymore. I hope you can develop some type of answer to what JAM and Patrick Caldon are saying. If not, then perhaps they are right and ID is just all wishful thinking.dougcampo
July 1, 2007
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Patrick Caldon, Thank you for your comment. I will look into it and the other examples you mention.jerry
July 1, 2007
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Well it looks as if JAM has completely discredited Behe's argument.dougcampo
July 1, 2007
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Why should these rare successes produce so much variety in the alleles of mammals especially humans.
Humans are probably the least polymorphic mammals if one factors in reproductive success.
NS and genetic drift drive the elimination or reduction in the variety of alleles.
Then how do you explain the amount of current polymorphism? Doesn't selection drive polymorphism in histocompatibility loci, for example?
Mutations that produce changes in the allele structure are relatively rare,...
I don't know what you mean by "allele structure." The two words don't go together in any meaningful way. -----
Jehu: At first I thought you were being incredibly disingenuous but perhaps you have only failed to logically follow the argument. Let me help you.
Thanks.
Since your comment at #25 you have taken the erroneous position that Behe claimed that Chloroquine resistance (CQR) requires mutations at K76T and A220S.
The specific substitutions don't matter for his calculation. The problem is that he claims that two are required, and that they have to occur simultaneously. It's an exponential error.
...Here are the quotes for the whole world to see. First from page 59: “Let’s compare the two numbers for the odds of achieving resistance to atovaquone, where just one mutation is needed, versus chloroquine, where (presumably – since if a single mutation could help, chloroquine resistance would originate much more frequently) two are needed. ”
His presumption is incorrect, because clinical studies don't look at origination (mutation). They can only detect mutations after they have been filtered through selection.
And from page 60-61: “The likelihood that Homo sapiens achieved any single mutation of the kind required for malaria to become resistant to chloroquine–not the easiest mutation, to be sure, but still only a shift of two amino acids...” Do you see anything in either of those quotes about CQR requiring mutations at K76T and A220S? No. Because Behe never makes the claim.
Behe claims that two amino acid residues must be changed in a single mutational event. There is no evidence to support his claim.
Behe’s position is that CQR requires at least two mutations.
...in one event, but there's not a bit of evidence to support that.
Although mutations at K76T and A220S are “almost always present” in CQR strains, Behe does not base his position of CQR requiring at least two mutations on the need for mutations at K76T and A220S but on the fact that CQR resistance arises so rarely.
But since we are limited to looking after many rounds of selection both for and against the mutant, we aren't looking at the frequency of mutational events at all. With all the experimental systems available, why did Behe choose one that lacks cell culture methods? Why not look at mutation rates in cultured human cells instead?
How rarely does CQR arise? Here is a relevant quote from page 59.
De novo by mutation? We don't know. Behe doesn't know.
Spontaneous resistance to atovaquone [just one mutation needed] can be found in roughly every third sick person. Spontaneous resistance to chloroquine can be found perhaps in every billionth sick person …”
There's a big difference between what happens and what we can find long after it has been filtered by selection.
The research backing up Behe’s position is as follows:
He'd have to look directly at mutation. There are plenty of systems (including human ones) in which he could have done that, but he chose to base the probability of human evolution on something that is ridiculously distantly reltated to us and in which we lack the ability to measure mutation rates.
“Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications.
What happens to any CQR mutants that originate in the mosquito phases, with no CQ around? They vanish. This is why White uses the terms "arisen" and "developing." It's not about mutation rates.
The single point mutations in the gene encoding cytochrome b (cytB), which confer atovaquone resistance, or in the gene encoding dihydrofolate reductase (dhfr), which confer pyrimethamine resistance, have a per-parasite probability of arising de novo of approximately 1 in 10^12 parasite multiplications (5).” N.J. White, Antimalarial Drug Resistance, J. Clin. Invest. 113:1084-1092 (2004).
So, let's read on from that point, shall we, and see who is doing the literature bluffing? But in the laboratory, much higher mutation rates than 1 in every 10E12 are recorded (12). What does that mean? Mutations may be associated with fitness disadvantages (i.e., in the absence of the drug they are less fit and multiply less well than their drug-sensitive counterparts). What does that mean in terms of extrapolating from appearance of resistance in a population to mutation rates? Another factor that may explain the discrepancy between in vitro and much lower apparent in vivo rates of spontaneous mutation is host immunity. Why does the author Behe cites (again, a review, demonstrating laziness) describe the ecological rates as "apparent," while Behe pretends that they are real?
Try to understand this JAM. Behe does not claim CQR requires mutations at K76T and A220S. Behe claims CQR requires two mutations. Behe bases this on the rarity of spontaneous CQR not on the explicit need for mutations at K76T and A220S.
I understand that. I also understand that there is no evidence supporting the claim that it requires two mutations. I also understand, as does the author of the paper Behe cites, that the rates of emergence of resistance in a population don't accurately reflect the mutation rate.
I would like to see one of Behe’s critics answer this question; if CQR can be achieved by single cumulative mutations, why has it arisen less than ten times in past fifty years?
Because the selection is intermittent at best, and reversed during each Plasmodium life cycle. I already noted this. Did you miss it? I'd like you to answer this question: why, given the availability of primary human cell cultures, did Behe choose to extrapolate from an organism whose mutation rate is impossible to directly measure, and which is very distantly related to us?
Art2: I’m wondering - is Behe using the review by White to argue that the frequency of occurrence of a double mutation is 1 in 10^20? Am I reading all of this - the discussion here, as well as EoE - correctly?
Apparently, despite the fact that White clearly understands that the emergence of CQR in a population is not a reflection of mutation frequency.
White derives the number by dividing the number of times de novo resistance has occurred by the population of the plasmodium under selective pressure of chloroquine resistance.
But White clearly realizes that this does not reflect the frequency of mutation.
It is a very simple and straight forward scientific observation that only those with a deep emotional commitment to Darwinism have trouble grasping.
White uses the verbs "developing" and "arising," not "mutating" to describe what happens in populations. White uses the term "mutation rates" to describe what is measured more directly. White also uses "apparent" to explain that the rate Behe is peddling as reflecting the mutation rate is not real, and explains additional reasons why CQR alleles will have trouble becoming established in a population: It is likely that this specific immune response directed against the immunodominant surface antigens will reduce the probability of the usually single mutant parasite ever multiplying sufficiently to transmit as for P. falciparum; there is only a 2–3% chance that the genetic event causing resistance would arise in the antigenically variant subpopulation that will expand to reach transmissible densities. Assuming an equal distribution of probabilities of spontaneous occurrence throughout the malaria parasites’ life cycle, the genetic event resulting in resistance is likely to take place in only a single parasite at the peak of infection. These genetic events may result in moderate changes in drug susceptibility, such that the drug still remains effective (e.g., the serine-to-asparagine mutation at position 108 in Pfdhfr that confers pyrimethamine resistance),... In the rare but important infection in which resistance arises de novo, killing of the transmissible sexual stages (gametocytes) during the primary infection does not affect resistance, because these gametocytes derive from drug-sensitive parasites. Gametocytes carrying the resistance genes will not reach transmissible densities until the resistant biomass has expanded to a population size close to that necessary to produce illness (>10E7 parasites) (38). Even if the resistant mutant does survive the initial drug treatment and multiplies, the chance that this will result in sufficient gametocytes for transmission is reduced as a result of both asexual-stage immunity (which reduces the multiplication rate and lowers the density at which the infection is controlled) and specific antigametocyte (transmission-blocking) immunity. Furthermore, other parasite genotypes are likely to be present, since infections are acquired continuously. These compete with the resistant parasites for red cells and increase the possibility of outbreeding of multigenic-resistance mechanisms or competition in the feeding anopheline mosquito. I highly recommend reading the White review; it is available online. There is nothing in it to suggest that the frequency of emergence of CQR Plasmodium represents the actual mutation rate, as Behe pretends it does.JAM
July 1, 2007
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Hi Jehu, Is there another link? The one you gave to the Drug Resistance Paper isn't working for me.Charlie
July 1, 2007
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Jehu, here's actually what White said: ""Chloroquine resistance in P. falciparum may be multigenic and is initially conferred by mutations in a gene encoding a transporter (PfCRT) (13). In the presence of PfCRT mutations, mutations in a second transporter (PfMDR1) modulate the level of resistance in vitro, but the role of PfMDR1 mutations in determining the therapeutic response following chloroquine treatment remains unclear (13). At least one other as-yet unidentified gene is thought to be involved. Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications. The single point mutations in the gene encoding cytochrome b (cytB), which confer atovaquone resistance, or in the gene encoding dihydrofolate reductase (dhfr), which confer pyrimethamine resistance, have a per-parasite probability of arising de novo of approximately 1 in 10^12 parasite multiplications (5). To put this in context, an adult with approximately 2% parasitemia has 10^12 parasites in his or her body. But in the laboratory, much higher mutation rates thane 1 in every 10^12 are recorded (12)." It sounds to me like White was estimating the frequency of occurrence of "productive" mutations in, not one, but three different genes (PfCRT, PfMDR1, and an unidentified gene). At the very least, this passage is very, very ambiguous. I'm not sure it means what everyone here is assuming.Art2
July 1, 2007
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