Saturday, August 12, 2006

Behe and the Dover “Literature Bluff”

So Who is Bluffing?

Useful links:

Barry A's original thoughts on the Literature Bluff here.
Barry A's further musings on the Literature Bluff here.
Wesley Elsberry's take on the Literature Bluff here.


"We can look high or we can look low, in books, or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system."

It was this proposition of Behe (Darwin’s Black Box p138, 2003 paperback ed) that the pile of books, articles and journals was intended to refute at the Dover trial and which Judge Jones mentioned in his opinion.

"However, Dr. Miller presented peer-reviewed studies refuting Professor Behe’s claim that the immune system was irreducibly complex. Between 1996 and 2002, various studies confirmed each element of the evolutionary hypothesis explaining the origin of the immune system."

What exactly did Behe mean?

The quote comes in the section of his book which examines the mechanism of the immune system looking at the complement pathway and the function and contruction of antibodies. (Chapter 6 – A Dangerous World)

In the concluding sections of this chapter Behe appears to be seeking to present the current understanding of the mechanism by which this system cam to exist. He maintains that the best efforts to do this are in two short papers:

1. David Baltimore’s 1994 article “Molecular Evolution of the Vertebrate Immune System.” PNAS 91, 10769-10770
Behe says that Baltimore suggests that the 3 sets of proteins are required for a functioning immune system (antigen receptors, antigen presentation molecules and the gene rearranging proteins.) They then argue that sharks have all three and note that immunoglobulin and TCR genes both require RAG proteins for rearrangement. On the other hand, RAG proteins (RAG is the component that rearranges the genes) require specific recombination signals to rearrange immunoglobulin and TCR genes. In this paper Behe notes that the authors speculate that a gene from a bacterium might have luckily been transferred to an animal. Luckily the protein coded by the gene could itself rearrange genes; and luckily in the animals DNA there were signals that were near antibody genes; and so on.

2. Farries, T.C., and Atkinson, J.P. (1991) Evolution of the Complement System. Immunology Today, 12, 295-300. In this paper the authors, says Behe, join Russel Doolittle in proposing unexplained proteins that are “unleashed” and “spring forth”

Behe acknowledges that there are other papers, articles and books on the subject but maintains that most of them are at the level of cell biology and are thus unconcerned about molecular mechanisms, or else they are concerned simply with comparison of DNA or protein sequences. He maintains that comparing sequences may be a good method to study relatedness, but the results can’t tell us anything about the mechanism that first produced the systems.

Behe complains that the papers fail to present quantitative calculations. He complains that they fail to acknowledge that gene duplications do not immediately make a new protein. He complains that none of them worry about the control mechanisms to regulate the pathway.

The “literature bluff” which was set up in the Dover trial presumably by Ken Miller presented a series of 8 articles in the pre trial documentation and a further "fifty- eight peer-reviewed publications, nine books, and several immunology textbook chapters" in the pile in the courtroom.

The question that I wish to ask is this… Who was right about the stack of papers. Behe mantains that these papers do not affect his proposition that the scientific literature has no answers to the origin of the immune system. Was Behe right when he made that proposition? Is he still correct?

So let us put this formally into what I will call the 3 pronged Behe test.

1. Do any of these papers present quantitative calculations showing a reasonable pathway for the origin of the immune system by non-intelligent means?
2. Do they acknowledge that gene duplication is different from new protein production?
3. Do they provide mechanisms for the origin of necessary control mechanisms to regulate the immune system pathways?

37 Comments:

Anonymous Hrafn said...

"Behe mantains that these papers do not affect his proposition that the scientific literature has no answers to the origin of the immune system."

1) Behe, by his own admission has not read these papers. Why then should we give any credence to what he says about their contents?

2) Behe is not an expert in either Immunology or Evolutionary Biology. Why then should we accept his assessment of the scientific literature in the intersection of these two fields over those of scientists who are (even apart from objection 1, above)?

3) In the latest edition of Darwin's Black Box, Behe fails to deal with the progress that has been made in this area since he originally wrote this book. The impression we are left with is that he cannot be bothered keeping up to date with it.

The issue is Behe's ignorance. This discredits him both as an expert witness and as an author.

11:05 am  
Anonymous Anonymous said...

All you clueless ID people talking about the evolution side "bluffing" are either ignorant or just insane, because the list of articles was put online here months ago:
http://www2.ncseweb.org/kvd/exhibits/immune/index.html

They also put up an annotated bibliography that contains quotes from and summaries of the significance of each article:
http://www2.ncseweb.org/kvd/exhibits/immune/immune_evo_annotated_bib.html

And then they put up an even bigger bibliography, showing that the trial list was just a fraction of what was available in the published literature:
http://www2.ncseweb.org/kvd/exhibits/immune/immune_evo_bib_long.html

...and then, they wrote it all up in an essay in the top peer-reviewed immunology journal, Nature Immunology. The essay summarizes the relevant evolutionary immunology and the role it played in the trial. NI put the essay on the web for free so that everyone could read it.
http://www.nature.com/ni/journal/v7/n5/abs/ni0506-433.html

All of this was broadcast on the evolution blogs months ago to make sure all you ID guys knew about it. And yet the ID bloggers don't even seem to be aware of it, or have some kind of mental filter that blocks painful contrary evidence.

This is a weird way to "bluff", putting all of your cards on the table for everyone to see.

The various ID bloggers who have been whining about "bluffing" in the last week or two simply have no clue what they are talking about. Are they really not aware of the above? If they *are* aware, why should anyone listen to their blather about "bluffing" unless they actually address the NI article and the listed literature? Anything else is mere assertion, or citation of Behe as if he is an authority on the par of the hundreds of evolutionary immunologists out there, which he isn't.

11:36 am  
Blogger Andrew Rowell said...

Annonymous & Hrafn,

You surely do not mind me asking the question: "Who is bluffing?" do you? I would have thought that you would be encouraging me to ask precisely these questions so that I will be personally confronted with the blindingly obvious conclusion that it is Behe who is bluffing.... Don't discourage me from doing what you surely want me to do!

11:51 am  
Blogger Andrew Rowell said...

In this post I am asking: what is Behe saying?
In the next I shall ask if he is right or not.

Are you happy that I have understood Behe correctly?

11:53 am  
Anonymous Hrafn said...

Andrew:

The flip side to the question of who is "bluffing," is which side has winning cards in their hand.

Evolution has a large number of papers and experts in Evolutionary Biology and Immunology. ID has Behe, who is an expert in neither, and hasn't even read the literature. It is crystal clear which side is bluffing!

12:55 pm  
Anonymous Hrafn said...

"Behe complains that the papers fail to present quantitative calculations. He complains that they fail to acknowledge that gene duplications do not immediately make a new protein. He complains that none of them worry about the control mechanisms to regulate the pathway."

If Behe had legitimate complaints to make, then the legitimate forum to make such complaints is the peer-reviewed scientific literature. Otherwise his complaints serve no purpose whatsoever.

"In this post I am asking: what is Behe saying?"

Given the level of obfuscation and equivocation that Behe is notorious for, it is hard to see what point he is trying to make, beyond obfuscation of his incompetence as an 'expert' witness.

"In the next I shall ask if he is right or not."

I would claim that he is "not even wrong" (to use the famous words of Wolfgang Pauli) - his claims are irrelevant, as he can neither substantiate them in a court of law nor in the peer-reviewed scientific literature.

Behe is nothing more than a clapped-out crank, repeating the same worn-out, debunked claims, as the world passes him by.

1:11 pm  
Anonymous Hrafn said...

"So let us put this formally into what I will call the 3 pronged Behe test."

No. Let us first inquire as to what qualifies Behe a partisan unqualified in either Immunology or Evolutionary Biology to establish a "test" of what is sufficient to confirm the evolution of the immune system.

Why should we take his word for it as to what should constitute "good enough"?

1:27 pm  
Anonymous Hrafn said...

This relevent comment turned up here:

"As the transcripts of the various sidebars show, these weren’t being entered “for the truth” of their contents, but simply to refute Behe’s claims that such work does not exist."

This clearly demonstrates that the articles weren't presented as a "literature bluff" but in order to call Behe's own bluff on the literature.

This also clearly demonstrates that BarryA's Rule 803(18) claims are flat out wrong!

11:49 pm  
Blogger allygally said...

hrafn said: "As the transcripts of the various sidebars show, these weren’t being entered “for the truth” of their contents, but simply to refute Behe’s claims that such work does not exist."

This clearly demonstrates that the articles weren't presented as a "literature bluff" but in order to call Behe's own bluff on the literature."


I said somthing very similar on the "Behe response to immunology stack" thread.

I said: "In any case the very existence of the articles shows that the field of immune biology is developing and that it provides at least prime facie evidence which Behe, if he was a serious person, would have read and been familiar with... don't you agree?"

The plaintiffs' lawyers called his bluff and he chickened out.
Anyone reading the full transcripts can easily see that Behe is a buffoon. I cannot understand why Andrew persists in defence of such a downright lazy and mistaken figure.

12:04 pm  
Anonymous Hrafn said...

Allygally:

The reason Andrew defends him is that Behe is one of the few figleafs giving ID even the slight appearance of having scientific legitimacy. If IDers were to admit that Behe is simply completely out of touch with scientific research, they'd be one step closer to having to admit that ID is simply Christian apologetics, of no scientific value.

12:48 pm  
Blogger Ian Musgrave said...

Andrew asks "Was Behe right when he made that proposition? Is he still correct?"

No, and no. Behe made the original claims by ignoring most of (and belittling the rest of) the original research in the field. His book was ironically published just as the transposon-like nature of V(D)J recombination was described (a direct prediction of the transposase hypothesis). I will once again direct readers to the annotated biography which gives a history of the key developments in the field, and the paper in Nature Immunology which also outlines the development of the field.

As for the three pronged test.
1. Behe wants an impossible amount of information, which no scientist could achieve. A mutation by mutation account, with selection coefficents attached to each step. What scientists have done (and this is what they do in all fields), is to make predictions based on the idea that V(D)J recombination originated by the incorporation of "free living" bacterial transposases, and confirmed those prediction (discovery of RAG elements, discovery of sequence homology to free living transposases, endogenous transposase activity etc. etc. see the anotated bibliography from more detail).

2. "Do they acknowledge that gene duplication is different from new protein production?" Irrelevant, as this is completely understood in molecular biology. It's like saying, "water is wet". And it is unproblematic, even Behe accepts that duplication and subsequent mutation produce new proteins with new function (for example the extented haemoglobin family, or the superfamily of enolases). Also doubly irrelevent, as it relates to copies of RAG transposases integrating with the genome, rather than producing anything new.

3. "Do they provide mechanisms for the origin of necessary control mechanisms to regulate the immune system pathways?" Why yes they do, see Marchalonis, J. J., et al., (2002). FASEB Journal 16(8): 842-848. for example. If Behe had actually read these papers, he might of understood what was going on, and not make foolish and uninformed blanket statements.

If we look at Behe's statement
"We can look high or we can look low, in books, or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system."

We can see that he was wrong then, and is even more wrong now, as an active research program that has made stunningly confirmed predictions provides a clear answer to the origin of the immune system.

3:24 pm  
Blogger Lifewish said...

Are you happy that I have understood Behe correctly?

Hard to tell - my personal view is that Behe is equivocating here. His claim, that "The scientific literature has no answers to the question of the origin of the immune system", is very grandiose and impressive-sounding. However, when pushed on it, he can happily retreat to the less-impressive "well, they haven't traced every single stage of the process in incredible detail yet..."

Personally, I wouldn't tend to jump on him too much for the original claim - it's fairly obvious from context that it's just a rhetorical flourish. I do worry, however, that people take him literally and underestimate the scope of scientific knowledge on this subject.

In this context, the stunt Rothschild pulled was merely amusing counter-rhetoric, tailored to demonstrate the mismatch between the tone of Behe's claims and their content.

Anyone got any strong views on this interpretation?

5:25 pm  
Blogger Andrew Rowell said...

Ian,

Thank you for your comments. Can I just respond to your point 3 at present? I think you must have posted the wrong reference. This one does not seem to be about the evolution of control systems at all and is not really a research paper at all. Can you check the reference?

10:53 pm  
Blogger Ian Musgrave said...

And a further clarification of my post in regard to point 1. Behe's request for "quantitative calculations" are there to make him look sciency to people unfamiliar with biology. In the case of the transpoases hypothesis, the key elements are yes/no answers. Either V(D)J rearrangement is mediated via transposition or it is not (it is). RAG elements are either transposases or they are not (they are), RAG elemnts are either highly similar to "wild" transposases or they are not (they are) and so on.

Behe also has a habit of focussing on short summary reviews (and making fun of them) rather than the technical reviews and orignal papers. He waxes indignant over a brefi summary review by Doolittle whic used the words "appears" a lot, ignoring the fact that the major point of the short review was to summarise the order of appearnace of key protiens, rather than detailed mechanistic studies.

And Doolittle has the last laugh. Jawed Fish lack the extrinsic clottig system, just as Doolittle predicted from evolutionary evidence, in addition jawless fish lack factor X and a slew of other clotting proteins, as predicted from evolutionary evidence.

So, evolutionary biologits, making predictions from evolutionary princilples, see their predictions confirmed and an "IC" system comes in reducible forms. What does Behe do? Ignore it.

11:13 pm  
Blogger Ian Musgrave said...

Andrew wrote:
"This one does not seem to be about the evolution of control systems at all and is not really a research paper at all."

It is a review paper which includes some of the control systems. Breifly, the adaptive immune system has simply co-opted the regulatory system for the non-adaptive innate immune system, for example by directly binding to CD45 (which predates the adaptive immune system) to activate NFkappa-beta. As the rearranging antibodies were derived from non-rearranging defese molecules that signal in this way (eg the APAR of hagfish), it is not surpising that they share the same signalling pathways. Indeed, with the deeper understanding of the Hagfish immune system, and invertebrated immune systems, it is readily apparent that the adpative immune system is an elaboration of the innate immune system.

2:46 am  
Anonymous Anonymous said...

So Behe concentrates on short review articles, but demands a wealth of detail on the mechanisms involved?

That strikes me as an extremely dysfunctional (and intellectually dishonest) literature search strategy.

Behe would appear to be seeking an obvious oxymoron: an in-depth summary. Yet further evidence that his position (both in court and in his writings) is nothing but a bluff.

4:07 am  
Blogger allygally said...

I think we are missing something fundemental here (pun not intended).

I'm not a scientist. One of the reasons I oppose the teaching of creationism as science is that, if you take the "revealed religion" route, you assume that you know the answers in advance and will therefore become lazy, and even willfuly blind, in pursuing new avenue of thought and evidence. This has implications, not just for science, but for all modern life and democratic insitutions in particular.

And THIS IS EXACTLY what Behe is doing here.

He says the literature shows he is right (although he hasn't read it) and the it "would be fruiless" to study it in detail. BECAUSE HE ALREADY KNOWS THE ANSWERS. God told him! So why waste time reading all that STUFF!

So this little vignette not only shows that Behe is lazy and incompetent, it shows that this stems from his underlying (religious) philosophical approach. Goddidit, why bother any further?

10:16 am  
Blogger Andrew Rowell said...

Ian,

If this is your answer to the Behe test -prong 3 then I would say that Behe is completely on target so far.

....A review article which says that the control system was co-opted intact from somewhere else!

10:53 am  
Blogger Andrew Rowell said...

Ian,

With regard to prong 1.

Your response is that Behe is asking for totally unreasonable detail when he asks for detailed accounts of possible mutations and selection pressures.

The first point here is that this is a tacit admission that there are no such accounts currently available and therefore that in the terms of his argument his first prong is technically correct.

The second issue is whether it is unreasonable to ask for such detail.

I am sure that you would like a situation where there is such detail and you certainly would not discourage students from seeking to research and present models which allow examination of possible pathways in this degree of detail.

The real issue is whether it is reasonable to doubt at this current moment in time that RMNS can achieve what has been claimed. Behe is convinced (or he appears to be convinced) that it cannot and he has done peer reviewed work in this area which is provoking discussion among scientists e.g Lynch's response.

Isn't this supposed to be how science works?

Behe is actually trying to do the sort of work which you claim is unreasonable and unecessary... and then claim that ID is a research stopper!

11:11 am  
Blogger Andrew Rowell said...

Lifewish,

With regard to the literature pile I tend to agree though I am sure that Ian will not and I am sure that Matzke et al will not.

With regard to the Behe rhetoric.. I do think that Behe's literature arguments in DBB carry weight and are a real gauntlet to anti-IDers.

Dismissing them as unreasonable demands for detail could be interpreted as a research killer.

His call for detailed mechanisms and realistic pathways is I believe a good and healthy stirring up of the grey cells.

12:19 pm  
Blogger Richard H said...

This comment has been removed by a blog administrator.

4:17 pm  
Blogger Richard H said...

Andrew,

This fundamentally comes down to one question...is Behe an expert in this field?

The answer is clearly no.

Although that does not mean he cannot ask for more detail, it does mean that he does not understand fully the current evidence and thinking behind the theory that he is asking for more detail on.

In any other field of science, no one would take seriously an individual who did not have a thorough understanding of the subject in hand, and who was also not considered to be an expert in that field, if they started to try and dispute a theory.

Behe is not up-to-date with the latest literature, and is not an expert in this field. How can he know whether the current evidence strongly supports the evolutionary theory or not, let alone start to question it? It is more likely it is his ignorance of the subject that has led him to reach a conclusion that things are too complex to have evolved.

4:20 pm  
Blogger Ian Musgrave said...

I'm busy setting up for this mornings lecture, so I won't be able to comment further until tonight but Andrew, let me get this straight...

Do you seriously contend that because the rearranging adaptive immune system uses the same control and signalling pathways the the non-rearrraging innate immune system, the thing that the adaptive immune system evolved from, this makes Behe right. If anything it shows how deeply he misunderstands biology. This is exactly what you would expect if the adpative immune system had evolved from the innate immune system by insertion of transposons into the hagfish APAR innate immunity receptor (and hence used the control mechanisms of the old APAR receptor). Co-option of existing stuctures is a dominant mode in evolution.

Oh, and Behe has done no work in this area. The Behe & Snoke paper is a theoretical work about neutral drift, not natural selection, and embarrisingly for ID shows that even if vertebrates were asexual clones (which slows things down a lot), they could develop new binding sites on proteins in the absence of natural selection in time compatible with the fossil record. Bacteria, which more closely resemble the simple model, could develop these features in a couple of years.

This work niether supports ID nor shws problems with natural selection (especially since NS is absent for mots of the model they use).

10:37 pm  
Anonymous Hrafn said...

In this post Dispatches from the Culture Wars discusses the unreasonable level of evidence that Behe demands - and the fact that he demands a far higher level of evolutionary evidence for his claimed IC examples than for evolved systems that he is willing to accept.

"But here's the problem with all of this: we can't produce that kind of detail, not only for any evolutionary explanation but for any historical claim of any kind."

3:11 am  
Anonymous Hrafn said...

"I do think that Behe's literature arguments in DBB carry weight..."

Andrew would you care to substantiate this assertion? The fact that Behe is neither an expert, nor particularly well-read in, the evolution of immunology, would appear to demonstrate the opposite view.

8:37 am  
Blogger Ian Musgrave said...

Here’s a little fable that may help people see the whole Behe thing more clearly. Suppose I wrote a book in 1995 where I stated that “We can look high or we can look low, in books, or in journals, but the result is the same, the scientific literature has no evidence of the existence of exoplanets.” Ironically, in that year the first definitive evidence of extrasolar planets is found. Fast forward to 2005, where I claim there is still no evidence of extrasolar planets. A pile of journal articles is plumped in front of me, listing the then 179 extrasolar planets (now 202) discovered. I’ve never read them, but confidently state they contain no evidence of extrasolar planets. The astronomers point to Doppler shift planets, transit planets, Doppler shift and transit planets, gravitational lens planets, but no, I insist that there must be a picture of the planets surface for me to accept that there are extrasolar planets. In vain the astronomers point to the spectra obtained of the atmosphere of extrasolar planets, no I insist on pictures of the planets surface. After this I confident say that “these papers do not affect my proposition that the scientific literature has no evidence of extrasolar planets”.

Just who is bluffing? Now insert Behe’s talking points, does this change your mind?

1:32 pm  
Blogger Ian Musgrave said...

Okay, I pulled a long night and early morning in the past day preparing for my big workshop (which failed to impress the students, sigh). So I’m going to bed now and ignoring substantial comment until tomorrow. I leave you with this paper, Strauch E, Beutin L. Imprecise excision of insertion element IS5 from the fliC gene contributes to flagellar diversity in Escherichia coli. FEMS Microbiol Lett. 2006 Mar;256(2):195-202. Basically, transponsons, not dissimilar to the transposons that form the RAG elements in modern immunoglobulin genes (IS5 rather than transib transposons, but similar), integrate themselves into the Falgellin gene, then get excised (in a manner reminiscent to that seen in immunoglobulin genes). The excision causes frame shifts in the flagellin gene, so the transcribed proteins are a little different to previous generations, which allows the bacteria to evade vertebrate immune systems that have produced antibodies to bacterial flagella (which is very common, flagellin is a major target of the immune system, does someone have to provide numerical estimates of selection coefficients before someone will accept that this is a beneficial thing?).

Now, if transposons can only be targeted to genes by our hypothetical (unseen unevidenced) Intelligent Designer (probably the Sirius Cybernetic Corporation), then we have the curious situation where the Designer gave vertebrates a system to avoid bacteria, and then the bacteria a system to avoid vertebrate immune systems. Talk about the right hand not knowing what the left is doing (Definitely the Sirius Cybernetic Corporation).

OTOH, if transposons can integrate into flagellin naturally, by natural mechanisms, then why can’t the RAG elements of the immune system have integrated naturally?

1:50 pm  
Blogger Lifewish said...

With regard to the Behe rhetoric.. I do think that Behe's literature arguments in DBB carry weight and are a real gauntlet to anti-IDers.

Dismissing them as unreasonable demands for detail could be interpreted as a research killer.


I disagree; scientists are demonstrably attempting to improve our level of understanding already. Demanding more detail than they can reasonably produce will have absolutely no effect on rate of research; it'll just royally annoy them. Like it or not, the ID movement has absolutely no impact in the scientific world of evolutionary biology.

On the other hand, accepting Behe's arguments as valid would by direct inference mean that all attempts to trace the evolutionary history of (for example) the bacterial flagellum were completely pointless. That would be a research killer.

In what way do you think Behe's arguments (which, IIRC, were mostly about irreducible complexity) have "real weight"?

His call for detailed mechanisms and realistic pathways is I believe a good and healthy stirring up of the grey cells.

The apparent belief that scientists were waiting to be challenged on this before getting involved in research, on the other hand, suggests a certain degree of deterioration of the aforementioned grey matter...

If there's an interesting, tractable question in a field, you can almost guarantee that at least one scientist will have addressed it. Remember, these are some of the smartest people on the planet, and they're competing to see who can answer the most questions.

12:35 am  
Anonymous Hrafn said...

Another matter weighing on the question of whether Behe's arguments "carry weight" is the forum he chose to make them in. Any crank with a PhD can write a book, and many have. Such works are typically subject to far less rigorous review than journal articles, and are thus not typically taken as seriously by the scientific community as journal articles.

By chosing this route, Behe has admitted that either he has no interest in having his arguments taken seriously by the scientific community, or that he knows his arguments are incapable of withstanding their scrutiny.

7:44 am  
Blogger Ian Musgrave said...

Andrew wrote:

"Dismissing them as unreasonable demands for detail could be interpreted as a research killer."

I don't know whether to laugh or cry at this statement. Behe's demands are not merely unreasonable, they are in principle impossible. His demand that we state the selective value as a quantitative figure requires us to resurrect late Cambrian jawless fishes. Now, non-ID scientists have reconstructed prehistoric rhodopsin, steroid receptors, retinoic acid receptors and hox genes (using techniques Behe has dismissed as pointless). The recent discovery that frozen mouse sperm survives for very long periods of time gives us hope that we may resurrect semi-mammoths. But late Cambrian jawless fishes are definitely off the menu.

Remember my fable? The demand for a picture of an exoplanets surface is not merely unreasonable, it is impossible. Even the amazing "planet finder" telescopes being designed now will never resolve an exoplanets surface. This hasn't stopped scientists from finding clever ways to detect exoplanets and their composition. Similarly it is evolutionary biologists that have invested over 10 years of painstaking and innovative research investigating the origins of the immune system, carefully looking for holes in their arguments and doing experiments from different angles to fill these holes. Where was Behe when all this was happening?
Behe was ignoring the whole thing.
“Q. And you haven't undertaken to try and figure out [the details of immune system evolution]?
A. I am not confident that the immune system arose through Darwinian processes, and so I do not think that such a study would be fruitful.”

The researchers who studied the evolution of the immune system, who have experimentally determined how it happened, and in the process worked out the mechanism by which antigenic rearrangement worked (no small feat in itself), found it very fruitful.

Who is the research killer here? Behe who does no research, and dismisses the painstaking work that has been done without even reading it? And to re-iterate, he makes demands that are not merely unreasonable, there are in principle impossible (not only do we have to resurrect late Cambrian jawless fish, we have to work out their population size etc.).

Even the mutation by mutation account he demands is impossible (in general but see the irony below). From the study of the transition of the TEM beta lactamase to cephalotaximase in bacteria, which happened over the past 10 years, and where we have the living organisms to study, we have found that there are multiple mutational paths to the final state. There is no "one true way" from one functional state to another. While we can reasonably infer the pathways in the case of neofunctionalisation of the steroid receptor and the retinoic acid receptor (ie we can give reasonable intermediates in an appropriate time frame, and even reconstruct a functional ancestral protein), we can't give the monolithic, linear, "one true pathway" that Behe demands.

The irony is that with the immune system, there is one key mutation, integration of a transib transposase into an APAR receptor gene (involved in innate immunity). We can describe this mutation quite well, and it fulfils Behe's challenge. The fused APAR-transib receptor used the same control mechanisms that the APAR used (and the evolution of this from very simple innate immunity systems is reasonably well understood), which fulfills the third arm of Behe's challenge. We can't give quantitative selection values, but that hasn't stopped real, non-ID scientists from trying to work them out in general. One could indeed say "It's the immune system, Duh! Anything that gives an organism an advantage over bacterial pathogens, however slight, will give an organism advantage". After all, the larges signatures of selection in the human genome are in the immune system genes, and re-arranging flagellin genes help bacteria evade our immune system. But scientists being what they are, picky folks, they have tried to analyze this in more depth. In the absence of being able to resurrect late Cambrian jawless fish[*], we can give general qualitative accounts of selectablilty of these traits (see Cohn below for an example, another paper Behe missed).

In the 15years since ID was first floated, ID has produced one theoretical paper that shows that neural mutation can produce complex binding sites (a bit of an own goal, that). In the 15 years since the modern version of the transposon hypothesis was first proposed, scientists have shown that RAG elements are transposons, will act as transponsons in the wild, have hunted down their nearest relatives and found the class of innate immunity receptors that they integrated with. It was real scientists, evolutionary biologists, who came up with testable models, worked out meaningful ways to test them, and carried out the tests. The ID response is to make a list of demands that are quite literally impossible to fulfill, while at the same time providing zero support for their ideas[**]. I ask again who the research killer here is.

Cohn M: At the feet of the master: the search for universalities. Divining the evolutionary selection pressures that resulted in an immune system. Cytogenet Cell Genet 1998;80:54-60 (DOI: 10.1159/000014957)

[*] Given the rate they are reconstructing ancestral proteins (and if the ID ideas are right, they shouldn’t be able to do this, but hey, they are), I give it 5 years before someone reconstructs the ancestral APAR protein and sticks a transib transposon in it. I predit that it will not be an IDer.
[**] The annual DI public relations budget would run my lab for 5-10 years, depending on how profligate I was with antibodies. Yet somehow they seem to avoid funding real research.

1:29 pm  
Blogger Andrew Rowell said...

Ian,

I am sorry I have got a little behind with your posts here... apologies.... and thank you for your efforts to educate me.

You said:
"Do you seriously contend that because the rearranging adaptive immune system uses the same control and signalling pathways the the non-rearrraging innate immune system, the thing that the adaptive immune system evolved from, this makes Behe right."

Yes. If the the control system was coopted intact from elsewhere we have done precisely nothing in explaining its origin.


You said:
"Behe has done no work in this area"

I did not intend to imply that Behe had done work in this area. I intended to be understood as saying that Behe is publishing the sort of paper that he said was absent from the immune system literature. Detailed consideration of particular changes on the pathway towards complexity showing that they are possible.

10:35 pm  
Blogger Andrew Rowell said...

Ian,
The exoplanet fable.

1. Prior to the publication of the papers the looking high looking low quote is valuable.

2. We need to compare the quality of the evidence which is claimed to amount to a proof or demonstration of fact.

10:44 pm  
Blogger Ian Musgrave said...

Andrew said:
" I am sorry I have got a little behind with your posts here... apologies.... and thank you for your efforts to educate me."

Never mind, life's like that. I have to slow down for a while due to work and family commitments (I have to spend my Sunday at the Universities Open Day).


Andrew wrote:
" Yes. If the control system was coopted intact from elsewhere we have done precisely nothing in explaining its origin."

For Zahrquons sake[*] Andrew, that is an amazingly silly statement. It's like stating that saying bird wings evolved from tetrapod forelimbs explains nothing, as we haven't explained tetrapod forelimbs (actually we have). What Behe is trying to imply, is that everything associated with adaptive immunity has to appear de novo, all at the same time (and hence is too complicated to happen). Since the adaptive immune system is a modification of the innate immune system, this completely undermines the force of that argument, as only relatively minor adjustments are needed, not the appearance of whole suits of things de novo. As for the evolution of the innate immune system, need I say that there is a huge literature on this, and the hagfish NFkappa-beta system is one end of a continuing elaboration of such systems since the first metazoans (which was in turn co-opted from much older NFkappa activated growth pathways).

Andrew wrote:
"You said:
"Behe has done no work in this area"

I did not intend to imply that Behe had done work in this area. I intended to be understood as saying that Behe is publishing the sort of paper that he said was absent from the immune system literature. Detailed consideration of particular changes on the pathway towards complexity showing that they are possible. "

Except that he hasn't done even this. All the Behe&Snoke paper (the ONLY paper) does is a simplistic examination of neutral drift. There are no detailed considerations of any changes whatsoever. It is almost, but not quite[**], completely unlike what he demands of immunologists.

Andrew wrote:
"Prior to the publication of the papers the looking high looking low quote is valuable."
Even for Behe's original statement in DBB, it was never true. Between 1990 and 1995 there were 19 peer-reviewed original papers on the origin of the RAG elements alone. I have ignored reviews, books and other aspects of adaptive immunity. These trace, with increasing sophistication, the development of the RAG –transposon hypothesis.

Andrew wrote: "We need to compare the quality of the evidence which is claimed to amount to a proof or demonstration of fact "

Well, Behe could never do that, as he never read these articles (he just got sarcastic about a very brief summary of the RAG-transposon hypothesis which formed the last paragraph of a perspectives article on the discovery of THC genes in sharks). But lets have a quick look at just the 1990-1995 papers, of these 19, 21% are published in Cell the 4th top paper in the world with an impact factor of 40.5, 37% are published in PNAS, Science and J Exp Med, all in the top 50 international journals with impact factors above 10, the remainder are almost exclusively published in specialist immunology journals with impact factors of 6 and above. In contrast Protein Science is the 170th ranked journal with an impact factor of 4.8 (not shabby but well below the quality of the journals RAG research was published in). So we have a record of consistent, peer-reviewed high-quality original research published in the top international journals.

Even in 1996, Behe's "high and low" statement was plain false. He couldn't have been looking very hard to miss the Cell papers, let alone the PNAS papers.

After 1996, with the publication of the paper showing RAG elements were transposases, there was an explosion of original peer-reviewed papers in the highest quality international journals (Cell, Nature, Science, J Exp Med). These papers confirmed and extended the previous work and tested and confirmed the predictions made by the transposon model. Of course, Behe knew nothing of this, he wasn't looking, despite papers being published where he said they would be if evidence for immune system evolution existed. When he claimed his position hadn't changed, this was a claim based on a combination of ignorance and impossible demands.


[*] Obligatory Hitch Hikers Guide to the Galaxy reference
[**] Another obligatory HHGTTG reference. Well, Behe&Snoke do look at mutations in abstract, but that is as close as they get to their demands of immunologists.

11:55 am  
Blogger Andrew Rowell said...

Ian,

Thanks for this.

How similar are the control systems for the non adaptive system as compared with the adaptive? Have you got papers which identify a route from one to the other?

12:37 pm  
Blogger Andrew Rowell said...

Ian,

You said:
"For Zahrquons sake[*] Andrew, that is an amazingly silly statement. It's like stating that saying bird wings evolved from tetrapod forelimbs explains nothing, as we haven't explained tetrapod forelimbs (actually we have). "

I do not see the comparison at all Ian. I inserted a careful qualification into my sentence involving the word "intact". If you said a bird wing came to be by coopting a tetrapod forewind intact then that would be an amazingly silly idea...I mean really funny! Can you imagine the poor bird!

Are you saying that lots of interesting stuff happened to the control system along the way of course? If so have we got at least some kind of feasible pathway from one to the other... or do I just have to take your word for it that it did happen.

We are using the word "origin" in a different way I think.

I want to see a scheme for the control of the non-adaptive immune system plus a scheme for the control of the adaptive immune system and a believable possible scheme for going from one to the other.
Is that demanding something unreasonable?

6:28 pm  
Blogger Andrew Rowell said...

Ian,

The RAG stuff is great, I like it. The comparison with the bacterial transposase is I am sure important and valuable. However you would (I am sure) agree that there needs to be more in the full story of the origin of the adaptive immune system than a suggestion that a transposase hit the right spot.

6:33 pm  
Anonymous Matt Inlay said...

By Andrew,
3. Do they provide mechanisms for the origin of necessary control mechanisms to regulate the immune system pathways?

Andrew, Behe's point about IC systems here is that all the parts would have to come together at once, including the control mechanisms. If the control mechanisms pre-existed prior to the insertion of the transposon into the ancestral antigen receptor gene, then his point (regarding the control mechanisms) fails. The two mechanims (VDJ recombination, and the control mechanisms) could have evolved incrementally, and not in "one fell swoop", as required for the basic IC argumentation.

The origin of the control mechanisms is an entirely separate issue, having its own rich history of research, as Ian pointed to.

2:48 am  

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