Behe vs Carroll, redux

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Over on the Ben Stine vs Intelligent Design thread , one Ben Major writes:

…..Behe just placed a major thumping on the head of Sean Carroll on pyrimethamine in a back and forth at Science for the full story see: http://www.amazon.com/gp/blog/A3DGRQ0IO7KYQ2

No, Behe just put together a series of non-sequiturs.

To put this in perspective, here is what Carroll wrote: (which flows on from this article )

“With respect to the latter, the passage he quotes in his Letter about how “[a]dding more mutations …. can increase the level of resistance” is immediately followed in his book by the disclaimer that “[h]owever, as usual there’s a hitch. Some of those extra mutations (but not the first one) seem to interfere with the normal work of the protein” (p. 75). Behe is clearly seeking to convey the message that there is some impediment to Darwinian evolution via multiple intermediates, both in this specific case and in general (hence the phrase “as usual”). However, this is not the case. Careful inspection of the data in the reference I cited (2 (Sirawaraporn et al., 1997)) reveals that, in fact, certain mutations (e.g., Cys59->Arg) increase specific parameters of the enzyme’s performance. Structural studies suggest that this mutation, found at very high frequency in drug-resistant parasites in nature, improves enzyme binding to substrates in the context of otherwise adverse mutations (3(Yuvaniyama et al., 2003)). Furthermore, pyrimethamine resistant dihydrofolate reductase enzymes actually have activities equal to or better than the wild-type enzyme (4(Sandefur et al., 2007)). Behe also neglects to note the fact that such triple and quadruple mutant enzymes have been found in isolates from India, Southeast Asia, Eastern Africa, and South America, including areas where pyrimethamine use has been limited. The latter suggests that mutant parasites may be as fit as wild-type parasites.”

What Behe writes in response:

“Carroll’s beef is that several papers he cites (W. Sirawaraporn et al., Proc. Natl. Acad. Sci. U.S.A. 94, 1124 (1997); J. Yuvaniyama et al., Nat. Struct. Biol. 10, 357 (2003); C. I. Sandefur, J. M. Wooden, I. K. Quaye, W. Sirawaraporn, C. H. Sibley, Mol. Biochem. Parasitol. 154,1 (2007)) have shown that, in the laboratory, in some respects intermediate mutations in the enzyme-target of pyrimethamine have better activity than the wild-type enzyme. But this data proves too much. If the mutations improve the enzyme in vitro, then that begs the question of why organisms with these mutations don’t outcompete the wild type in nature, even in the absence of pyrimethamine.”

This is a clear example of misdirection. Firstly, the context is clearly is whether the extra mutations that increase the resistance of the malarial parasites are deleterious to enzyme activity, and whether further increases in resistance can only be supported if two subsequent mutations occur together (Behe’s claim, pg 75 EoE), or if all the mutations increase fitness in a stepwise fashion (Carroll’s claim), not whether Behe made any mention of pyrimethamine resistance at all. As it happens, the data support Carroll, experiments in enzyme activity clearly show that mutations in the enzyme-target of pyrimethamine result in step-wise increases in resistance, with no detrimental effect on the enzyme activity (even a modest increase in activity).

Mutation Enyme activity vs wild type increase of resistance vs wild type
S108N similar 10x
S108N+N51I 2x 20x
N51I+ C59R+S108N 2x 100x
N51I+C59R+S108N+I164L 2x 700x

Behe writes:

“One possibility, which plagues all in vitro work, is that perhaps the mutants have other, detrimental aspects, not measured in an assay, which makes the alteration a net burden in the wild. If that is the case, then the mutant enzyme might run rings around the wild-type enzyme when both are in a test tube in a lab, but could still be a bust in nature. “

Unfortunately for Behe, the fitness of the double and triple mutants have been measured in the field, and the S108N+N51I and N51I+ C59R+S108N mutants are more fit than the wild type (Roper et al., 2003). Behe asks why “organisms with these mutations don’t outcompete the wild type in nature, even in the absence of pyrimethamine”. Well, they do. In Tanzania, resistant malarial parasites spread into areas where no drug was being used, up to 150 miles away from drug using villages (Clyde & Shute 1957). In South-East Asia, the triple resistant mutants are still highly prevalent, decades after pyrimethamine use has been discontinued (Sanderfur et al., 2007). The same pattern is seen around the world, where pyrimethamine is discontinued, very many years later, the wild type has still not displaced the mutant parasites. The mutant enzyme is running rings around the wild-type enzyme in the wild.

In the paper Behe cites as hypothesizing that multiple simultaneous mutations (Nair et al., 2003), he fails to note that this was one of three hypotheses presented in that paper (selective bottlenecks, small effective population size were the two others), and the multiple mutations hypothesis was based on an incorrect fitness estimate for multiple mutations (see Sanderfur et al., 2007). As well, pyrimethamine resistance develops very rapidly, 6 years from the first appearance of resistance to fixation of 3 or 4 mutation-bearing enzymes is typical (Sanderfur et al., 2007, Talisuna et al., 2004). This is not consistent with the need for simultaneous double mutations (Talisuna et al., 2004).

Thus once again, Behe misdirects and misleads by only selectively reporting or interpreting data, or failing to understand the data. Carroll has it right; acquisition of pyrimethamine resistance is an example of stepwise accumulation of beneficial mutations.

References:
Carroll S, Science 316, 1427 (2007)
Carroll S, Science 318, 196 (2007)
Clyde, DF, and Shute TG. Trans. R. Soc. Trop. Med. Hyg. 51: 505–513. (1957).
Nair S., et al., Mol. Biol. Evol. 20(9):1526–1536. (2003)
Roper, C., et al., Lancet 361, 1174–1181. (2003).
Sandefur CI, et al., Mol. Biochem. Parasitol. 154,1 (2007).
Sirawaraporn W, et al., Proc. Natl. Acad. Sci. U.S.A. 94,1124 (1997).
Talisuna, AO, et al., Clinical Microbiology Reviews, 17, p. 235–254 (2004).
Yuvaniyama J, et al., Nat. Struct. Biol. 10, 357 (2003).

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21 Comments

Thanks for this Ian. Slightly off this topic but still on Behe vs Carroll, I thought I’d raise a question that I’ve been wondering about for a little while. In Behe’s original response to Carroll’s book review he writes:

In his enthusiasm Carroll seems not to have noticed that, as I discuss at great length in my book, no protein binding sites — neither short linear peptide motifs nor any other — developed in a hundred billion billion (1020) malarial cells. Or in HIV. Or E. coli. Or in human defenses against malaria, save that of sickle hemoglobin. Like Coyne, Carroll simply overlooks observational evidence that goes against Darwinian views. In fact, Carroll seems unable to separate Darwinian theory from data. He writes that “what [Behe] alleges to be beyond the limits of Darwinian evolution falls well within its demonstrated [my emphasis] powers”, and “Indeed, it has been demonstrated [my emphasis] that new protein interactions (10) and protein networks (11) can evolve fairly rapidly and are thus well within the limits of evolution.”

Yet if one looks up the papers he cites, one finds no “demonstration” at all. Those papers show, respectively, that: A) different species have different protein binding sites (but, although the authors assume Darwinian processes, they demonstrate nothing about how the sites arose); or B) different species have different protein networks (but, again, the authors demonstrate nothing about how the networks arose). Like Jerry Coyne, Sean Carroll simply begs the question. Like Coyne, Carroll assumes whatever exists in biology arose by Darwinian processes. Apparently Darwinism has eroded Coyne’s and Carroll’s ability to separate data from theory.

I very briefly took a look at references 10 and 11 and from my quick scan, I wonder if maybe Behe has a point. Here are references 10 and 11.

http://www.pnas.org/cgi/content/full/102/39/13933

Here is reference 11:

http://compbiol.plosjournals.org/pe[…]025&ct=1

This actually relates to the final point Behe makes in his most recent point, where he writes:

If there is a “massive literature” on the evolution of protein-protein interactions which is pertinent to the questions I raise, Sean Carroll somehow failed to cite any of it in his review.

Any thoughts would be much appreciated.

I have mixed feelings about this kind of discussion. Of course, I appreciate it that scientists are enlightening us about the realities concerning evolution. So I’m certainly not complaining. Yet the anti-evolutionists can only delight in the appearance that they have generated - the appearance that there is something substantive to ID that leads to scientific “controversy”. Or, to put it another way, what connection is there between a (supposed, but not really existing) hypothesis of “intelligent design” and what Behe is claiming? How does Behe’s claim differ from just yet another “gap in evolution”. How does Behe’s claim amount to support for an alternative hypothesis?

Tom S Wrote:

How does Behe’s claim amount to support for an alternative hypothesis?

It doesn’t, and he knows it. Otherwise he’d be saying “Here’s where, when and how we think the design actuation event occurs, and here’s how I’ll test it, and here’s how one can falsify it - without having to account for the whereabouts of every atom in the last 4 billion years (which is the only way to falsify ID now).” Instead the best we get is (1) that the malaria parasite was designed (& I’m not sure if he even commits to that), and (2) families (or was it orders?) and up, and maybe even genera, were designed at some point - which could be at the beginning of life, Cambrian, but that’s not ID’s to find out.

They could say even less than that, but ID leaders like to throw out a few bones now and then, including letting lackeys like Ben Stein admit that the designer is God, then sit back waiting for their critics to provide more quotes to mine.

In South-East Asia, the triple resistant mutants are still highly prevalent, decades after pyrimethamine use has been continued.

discontinued?

Instead the best we get is (1) that the malaria parasite was designed

They want people to think that God intentionally designed parasites? I have yet to figure out why they seem to want people to think that.

Henry

Henry J:

Instead the best we get is (1) that the malaria parasite was designed

They want people to think that God intentionally designed parasites? I have yet to figure out why they seem to want people to think that.

Henry

Because the Intelligent Designer of parasites is actually Satan?

Henry J plaintively asked: “They want people to think that God intentionally designed parasites? I have yet to figure out why they seem to want people to think that.”

To paraphrase biologist J B S Haldane, “God must have an inordinate fondness for parasites, because he created so many of them.”

They want people to think that God intentionally designed parasites? I have yet to figure out why they seem to want people to think that.

Two things: chutzpah, and the attempt to steal away a powerful argument against “design”. Behe also gets to pretend that he’s doing science in the bargain, because he’s not just trying to say that birds’ wings are designed, he’s ‘following the evidence’ (like ID as a “science” is supposed to do) to claim that P. falciparum is designed.

But mainly it exists to rhetorically neutralize the question of what the purpose and the design of malaria is all about. These are legitimate questions to be asked of any IDiot who claims that life is too complex to evolve, and (using their false dilemma) ‘must therefore have been designed.’ Behe knows of nothing that can point to design in P. falciparum, or in anything else, not purpose, rational solutions to problems, nor any kind of value that P. falciparum must have to the telos that Behe believes in, human life. However, rather than admit that he has absolutely nothing but attacks on the evolutionary theory within which P. falciparum makes imminent sense, he diverts attention to his failure by using his bogus “facts” to insist that nevertheless P. falciparum was designed.

Thus it is a rhetorical move to divest a strong argument against design of its force, since he cannot face the issue head-on. No doubt it does not sit well with most creationists or even most IDists, but they’re not going to say too much because they need Behe’s fluff and diversions since they are even less adept at word games than Behe is. And sure, it doesn’t really work with any scientists, however it does force reviewers to argue against the “design” of P. falciparum, rather than to point out the most obvious fact of all, that P. falciparum is a counterargument to any honest ID theory. There being no honest ID theory at present, it is a good tactic for the pseudoscientists to concentrate the attacks upon their highly dishonest proposals, rather than to allow ‘ID critics’ to point to the total lack of any design theory which can account for P. falciparum.

Glen D http://tinyurl.com/2kxyc7

They want people to think that God intentionally designed parasites? I have yet to figure out why they seem to want people to think that.

Let’s also remember that the social and political goals, and the ostensible religious interpretation, of ID/creationism supporters, are often grounded in harsh, punitive, arbitrary, and even sadistic authoritarianism (with themselves as the earthly authorities, of course).

From my perspective, the idea that malaria was designed because sinful humans deserve to suffer is outrageous, especially given the obvious fact that malaria infection is unrelated to sinfulness.

To some creationist minds, however, this idea is probably quite appealing.

By the way, if you think I’m being unfair, why don’t you wait and see if any creationists disagree with me.

noncarborundum said:

discontinued?

Yep, fixed. Thanks for that.

Dale Husband Wrote:

Because the Intelligent Designer of parasites is actually Satan?

Yeah, and who designed Satan? Is this the deity’s excuse when he screws up (da debbel made me do it!)?

Ian, it seems to me that in the very comments he makes, Carroll is pointing to the problem that Behe goes on to highlight; i.e.,

Careful inspection of the data in the reference I cited (2 (Sirawaraporn et al., 1997)) reveals that, in fact, certain mutations (e.g., Cys59->Arg) increase specific parameters of the enzyme’s performance. Structural studies suggest that this mutation, found at very high frequency in drug-resistant parasites in nature, improves enzyme binding to substrates in the context of otherwise adverse mutations (3(Yuvaniyama et al.)

IOW, the protein binding is overly strong. Parasites might in fact be parasitic because they can, with regards to the host, preferentially bind themselves to certain enzymes; while this might be good for the parasite, the augmented strength of the interaction might, in general, be bad for the host; hence, Behe writes asks about why we don’t see this stronger binding in vivo.

“thumping on the head”

this is the problem. it takes more than just good arguments because the true believers will watch one argument and report seeing a completely different one. Creationists. Can’t live with ‘em, can’t kill ‘em.

snaxolotl Wrote:

Creationists. Can’t live with ‘em, can’t kill ‘em.

How do you know this to be so? Have you tried?

i dont mean to pour cold water on what is obviously a joke, but talking like that just allows religious fundamentalists to label freethinkers as “militant atheist fundamentalists” whilst providing them with a documented occurrence of death threats to use in their quote mines.

James, I see your point, but if the IDologists were going to construe what I wrote as a death threat, they could just as easily take anything else negative that I’ve said in the same vein. After all, their track record in twisting quotes so they mean the opposite of what the author intended is well known.

I thought I’d raise a question that I’ve been wondering about for a little while.

SteveF, in fact you raised the question here before.

Both wamba and I answered to the effect that Behe excludes observed evolved protein-protein interactions (as Musgrave, ERV, et al have discussed), for example by they or their genes occurence before adapting to humans.

The answer you gave is:

In general terms I agree with the thrust of your argument. It’s not reasonable for Behe to demand that every single step in a pathway be provided or direct evidence for precisely which pathway was taken.

However, this is a seperate issue. What interests me here is that Carroll puts forward references to support his claim that new protein interactions and networks can evolve pretty easily (I provide links to the relevant articles). Behe disputes that these papers provide such evidence, not simply handwaving them away as showing insufficient detail (his usual trick), but by arguing that they simply do not support Carroll’s case (i.e. no evidence to show how networks or sites evolved).

I now did as you, quickly scanned Carroll’s text and the two references.

Carroll says:

… Furthermore, any pair of interacting proteins can readily recruit a third protein, and so forth, to form larger complexes. Indeed, it has been demonstrated that new protein interactions (10) and protein networks (11) can evolve fairly rapidly and are thus well within the limits of evolution.

And indeed ref 10 has a phylogenetic tree of proteins (Fig.1.) interacting with different substrates, and ref 11 claims to show rewiring of protein networks. They seem to show or even discuss outright the rate of these processes. I will assume for the purpose of the discussion that they are correct and show rates consistent with observations.

In that case it remains Behe’s claims on what Carroll and the paper says. No, I don’t think the papers show that “different species have different protein binding sites” or that “different species have different protein networks”, as Behe claims. They show that evolution happened and discuss evolutionary pathways and their rates, as Carroll described.

What is perhaps missing is to pin down the exact historical pathway? But you conceded that it was unreasonable.

I guess I’m unsure exactly what you think Behe’s point is. As I see it he outright rejects the evolutionary processes that are described and tested. And that is besides the point. :-P

Um, two formal matters.

I have sometimes used italics for names, and it wasn’t intended above as a marker for emphasis. [I will have to come up with a different praxis as it was confusing.]

And the quoted part of your answer above was to wamba.

harold wrote:

“From my perspective, the idea that malaria was designed because sinful humans deserve to suffer is outrageous, especially given the obvious fact that malaria infection is unrelated to sinfulness.”

Actually, malaria deaths are disproportionately very young children. So, sinfulness is related to malaria infection– They’re negatively correlated.

Even if Behe’s point were proved, and there really were an Intelligent Designer who took some kind of twisted pleasure in killing off little kids, is there any threat or any promise at all that could possibly make you want to worship such a being?

Behe asks why “organisms with these mutations don’t outcompete the wild type in nature, even in the absence of pyrimethamine”. Well, they do.

Ok… In that case, why did the variants not evolve and displace the current wild type before the pyrimethamine challenge? I.D. has an answer of a sort (the (malevolent) designer never thought of the mutations until we started getting uppity), but what does evolutionary theory have to say?

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This page contains a single entry by Ian Musgrave published on October 24, 2007 4:20 AM.

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