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Author
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Topic: Intelligently Designing Immunity
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Nel
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Member # 614
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posted 07. April 2003 18:12
In this post I'm going to lay out positively what I think points to intelligent design of acquired immunity by using Behe's thesis of irreducible complexity and try to respond to common criticisms of his discussion. This is a very rough draft of a version I am working on that contains some material I will not post on the internet until I'm finished. This initial draft is by no means the final one. This is also unofficial, I'm new to the whole origins debate, so those are my caveats.
In Darwin's Black Box (1996) Behe begins by discussing clonal selection.
All immunoglobins recognize and bind specifically to a an epitope on an antigen.B cells are initially activated to secrete antibodies after the binding of antigens to specific membrane Ig's. After that, the B cell gets the signal to make a secreted form of Ig, which activates the response to attack the foreign invader.
He notes that the required components are:
quote:
(1)the membrane-bound form of the antibody;(2) the messenger; and (3) the exported form of the antibody.
With respect to the difficulty this poses for Darwinian evolution, Behe writes:
quote:
A cell hopefully trying to evolve such a system in gradual Darwinian steps would be ina quandary. What should it do first? Secreting a littel bit of antibody into the great outdoors is a waste of resources if there's no way to tell if it's doing any good. Ditto for making a membrane-bound antibody. And why make a messenger protein first if there is nobody to give it a message, and nobody to receive the message if it did get one? We are led inexorably to the conclusion that even this greatly simplified clonal selection could not have come about in gradual steps.
... all three ingredients had to evolve simultaneously. Each of these three items - the fixed antibody, the messenger protein and the loose antibodies - had to be produced by a separate historical event, perhaps by a coordinated series of mutations changing preexisting proteins that were doing other chores into the components of the antibody system. Darwin's small steps have become a series of wildly unlikely leaps. Yet our analysis overlooked many complexities: How does the clel switch from putting the extra oily piece on the membrane to not putting it on? the message system is fantasically more complicated then our simplified version. Ingestion of the protein, chopping it up, presenting it to the outside on an MHC protein, specific recognition of the MHC/fragment by a helper T cell, secretion of interleukin, binding of interleukin to the B cell, sending the singal that interleukin has bound into the nucleus - the prospect of devising a step by step pathway for the origin of the system is enough to make strong men blanch.
Matt Inlay's response to this was that a TCR is basically an antibody that is membrane bound. Thus, so the argument goes, an antibody does not need (3) and thus is not IC. However, just as B cells synthesize and release antibodies, the T cells synthesize and release cytokines. These cytokines, which are soluble mediators, tell the other cells to activate and eventually eliminate the antigen. That is, they release cytokins that provide various activation signals for the B cells. Moreover, not only do TCR only recognize MHC/peptide (as opposed to the more flexible antibodies which circulate), but going to the antigen directly by the TCR is not sufficient. You need to signal the binding of the TCR to the antigen which must be done in a specific way, and you have to signal the ligation of stimulatory molecules. After that you have to get through very complex steps to release the cytokines. They come in contact with their receptors and do their job.
Inlay's next point in response to Behe's discussion of Clonal Selection has to do with a point I have centered on before:
quote:
It remains unclear whether a TCR-like gene appeared first or an Ig-like gene. However, it is also possible that the ability to rearrange came after the evolution of the alternative splicing pattern, resulting in the ability to switch. This would require that antigen receptors with a single specificity be effective mediators of immunity. Could this have occurred? Absolutely.
However, as I pointed out elsewhere, both and Inlay and charlie d blundered on this point. It is unlikely that any innate receptor have single specificities. For example, the macrophage scavenger receptor recognizes ac-LDL, altered forms of bovinew serum albumin, pI:pC, and more. TLR4 has LPS and RSV-fusion protein, a still unidentified lipid from TB, Hsps, etc. Hemolin is not only a bad choice for a precursor to antibodies, but it is also a generic binder. Which brings me to the next section.
Behe points out that the antibody-diversity system, which consists of the V(D)J recombinase (and homologous recombination in some animals) and receptors, is irreducibly complex.
I think Behe's point here is that there is a dangerous gap between the jump from innate immunity to acquired immunity, acquired immunity is largely successful because it can generate specificity for any kind of foreign substance. Innate immunity cannot. And then there's the fact that if innate immunity consisted of receptors with single specificities, then the likelihood of a foreign substance being recognized diminishes. Even if there are some innate receptors or something like them, with single specificities, a handful of them wouldn't be enough. Which is why Behe says that a system with only a few antibodies are "not sufficient to make a difference". Bacteria would likely be able to evade, or develop resistance to those few antibodies. It has to make a lot and it has to make them fast. Going back to the whole issue of the specificity of the receptors, when Inlay mentions innate receptors, he is strenghthening Behe's point, not weakening it, since he is pointing to generic binders, not specified binders.
As an aside, a brief response to Charlie d, who wrote:
quote:
I would add to Rex's comment on horseshoe crabs that lobsters are known to live up to 50 years, octopi for several years, some insects for decades. On an innate immune system.
Horshoe crabs only live for 25 years at best. Lobsters actually live up to 15 years, with some exceptions going up to 50. Life span of octopi is 3 years at best. Not sure why he brought octopi up. I would be interested to see which insect lives for "decades". I wouldn't be surprised if there are execptions to the statement I laid out when I said large vertebrates typically live longer, I wouldn't be surprised if there are exceptions among invertebrates because they have a generic binding immune system. The problem is an organism with "a few antibodies" with single specificities. This requires a series of lethal unselectable steps.
A receptor with a single specificity can be bypassed or adapted to by a bacteria. There is also the problem of the loss of those receptors with single specificities through stochastic evolution. Which means if a pathogen whom that specific receptor was acting as an antibody for disappears from the population for a while, a mutation occurs where loss of that specied innate receptor or group of specified innate receptors are now gone, this is inherited in a population, the pathogen comes back, they all die.
With those organisms that just have innate receptors, or even one or two antibodies, are in an arms race that may be too much for them. Just as the Red Queen said, "Sometimes it takes all the running I can do to stay in the same place." At least thats Behe's point. I think thats why it's most parsimonous to say that it arrived in large vertebrates or at least was in wait for large vertebrates. Dr. Peonie makes a good point:They are just examples.
As the paper of David Baltimore et. al. stated in Molecular Evolution of the Vertebrate Immune System :
quote:
immunoglobulin and TCR genes both require RAG proteins for rearrangement. On the other hand, RAG proteins require specific recombination signals to rearrange immunoglobulin and TCR genes
Proc Nat Acad Sci, 91,10769-10770
quote:
At the heart of the combinatorial immune system are the RAG1 and RAG2 genes. These genes are:
A. Not related to each other.
B. Highly conserved in vertebrates
C. Responsible for the only known site specific recombination in vertebrates
D. Not present in agnathans or lower eukaryotes.
The similarity of RAG1 to bacterial transposases, the absence of introns in the RAG genes and their abrupt appearance in sharks has led to the suggestion that these jumped into the genome as a lateral gene transfer event. If so this is a remarkable story – that two different genes jumped into the germs cells of an agnathan, integrate into an Ig molecule and then generate the diversity of antibody and TcR molecules. At essentially the same time we get the MHC genes (see below) and probably the jaw and thymus to boot.
Gellert, M. 2002. V(D)J recombination: rag proteins, repair factors, and regulation. Annu Rev Biochem. 71:101-32.
Bartl, S., D. Baltimore, and I.L. Weissman. 1994. Molecular evolution of the vertebrate immune system. Proc Natl Acad Sci U S A. 91:10769-70.
Laird, D.J., A.W. De Tomaso, M.D. Cooper, and I.L. Weissman. 2000. 50 million years of chordate evolution: Seeking the origins of adaptive immunity. Proc. Natl. Acad. Sci. U.S.A. 97:6924–6926.
The fact that Rag1 and Rag2 was acting as a transposase before jumping into an organism, interacting with Ig and TCR molecules, and at roughly the same time we get MHC, the jaw, and thymus suggests strongly that what we are seeing is an intelligently designed event which can be called "The Big Bang" of acquired immunity.
quote:
In jawed fish and all "higher" vertebrates, adaptive immunity is possible because of what I like to think of as the immunological "Big Bang," which occurred in some ancestor of the jawed fish.
Janeway: Immunobiology, 2001
As mentioned already, this is true for sharks and rays as well, in that it appears all at once.
With respect to the complement cascade, Behe had this to say:
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It is the control systems that are the problem. At each control point both the regulatory protein and the masked protein that it activates have to be present from the beginning. If C5b were present, the rest of the cascade would immediately be touched off; but if C5 were present with nothing to activate it, then the whole pathway would always be shut off. If C3b were present, the rest of the cascade would immediately be touched off; but if C3 were present with nothing to active it then the whole pathway would always be shut off.
And this relevant point to much of the criticism out there.
quote:
[b] Even if one imagines a much shortened pathway (where, say, C1s directly cuts C5), insertion of additional control points into the middle of the cascade runs into the same problem: the irreducible complexity of the switches.
The components for complement are C1, C4, C2, C3, C5, C6, C7, C8, and C9 this is the classical pathway.
The alternative pathway uses C3b,factor B, factor D, properdin, C3,C5, C6,C7, C8, and C9.
In the lectin pathway, there is a protein with structure very similar to C1q,along with MASPs.
To activate the complement cascade, thematically, it requires three steps, recognition, enzyme activation, and expression. The three pathways have different proteins and enzymes for the first two steps, however what results is the same for all three.
Be stated:
quote:
In the complement pathway, both C3 and C4 have unusual, highly reactive internal groups that chemically attach to the membrane after the proteins are cleaved by other factors. These special features have to be avialble before the pathway is functional.
Activation of C3 is an important, and common, step in all three of the complment cascades.
The activation through the classical pathway requires C1q, the alternative pathway requires C3b, properdin, and serum factors B and D; and the lectin pathway requires binding carbohyrdate residues on the surface of the bacteria similar to C1q. Although, very little is known about the lectin pathway at this point.
If C1, C4, or C2 are missing there is a risk of developing SLE. When C3 is depleted because there is uncontroled activation of the alternative pathway the organism is susceptible to infections. Since C1NH controls C1r and C1s (I can't put the lines on these things), uncontrolled cleavage of C2 and C4 results.
Let me close with an important final point by Behe:
quote:
...I have looked at three features of the immune system - clonal selection, antibody diversity, and the complement system - and demonstrated that each individually poses massive chalenges to a putative step-by-step evolution. But showing that the parts can't be built step by step only tells part of the story, because the parts interact with each other. Just as a car without steering, or a battery, or a carburetor isn't going to do you much good, an animal that has a clonal selection system won't get much benefit out of it if there is no way to generate antibody diversity. A large repertoire of antibodies won't do much good if there is no system to kill invaders. A system to kill invaders won't do much good if there's no way to identify them. At each step we are stopped not only by local system problems, but also by requirements of the integrated system.
Of course I left out more discussion of the how the immune system distinguishes between self and non-self which is also very complex. In fact, I left out a great many things. But thats all I have time for and should be enough to get some kind of conversation going.
[ 07. April 2003, 18:16: Message edited by: Nelson_Alonso ]
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charlie d.
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posted 07. April 2003 19:05
Oh geez, for the last time.
Point 1: Soluble antibodies are normally administered i.v. to immunodeficient subjects who cannot make their own. This allows these patients to conduct almost normal lives. That is, soluble antibodies, "secreted in the great outdoors", in the absence of clonal selection, or membrane-to-soluble transition, are effective immune mediators after all (enough to produce a selective advantage). Similarly, cell-bound antigen receptors are effective in improving phagocytosis in invertebrates. Whether vertebrtae antigen receptor precursors were secreted or membrane, cells bearing them did not have any difficult choice to make.
Point 2: As I discussed ad nauseam in the other thread, antibodies in sharks are low affinity and polyspecific, and so are polyspecific natural antibodies which play an essential role in our own immune system. Looks like polyspecific antibodies are quite effective immune mediators after all (enough to produce a selective advantage as primitive antigen receptors).
Point 3. Moreover, shark antibodies definitively disprove the idea that single-antigen specificity is the main function of the somatic recombination system. Somatic recombination mediated by RAG proteins existed for tens of million of years before single-specificity antibodies (which depend on somatic hypermutation and clonal selection) arose. That is, even assuming the RAG system is IC, its "basic, and therefore original function" (Dembski's words) simply cannot be the generation of single specificity antibodies.
Point 4. Inlay and charlie d did not blunder in pointing to innate antigen receptors, simply because the "single specificity" is an artificial clause that has no bearing on immune function, but only on the construction of contrived hurdles to evolutionary paths. As long as polyspecific receptors (of the innate or shark Ig kind) are effective at mediating immune responses, that's all that matters to an organism (and to evolution).
Point 5. I am missing what Nelson's problem is with Inlay description of complement evolution: are there or are there not complement cascades that lack one or more of the supposedly IC steps? So, where is the problem of the "insertion of the switches"?
Now, I think we have beaten this dead horse long enough. The argument for "ICness" of the immune system depends entirely on a basic ignorance of the system's features, and - probably as a consequence - on the systematic replacement of simplistic functional schemes and diagrams, relevant only for the rhetorical sake of an antievolutionary argument, for actual biological functions and selective needs of organisms, which are what is relevant to biology and evolution. Indeed, in the previous thread, Nelson had to undergo multiple twists, gyrations and additions to his definitions to reach an argument that is logically consistent with his preordained theoretical goal, and I am quite sure more twists, gyrations and additions will follow.
Ultimately, however, the only thing that matters is that, since the publications of DBB, research based on evolutionary hypotheses has highlighted a number of interesting aspects of immune system function and its origins, and that the more we learn the more we find functional and structural intermediates, variants and precursors for the various components. Nothing of this would have happened if we had just given up and appealed to design, as Behe and Nelson would want us to.
[ 07. April 2003, 19:08: Message edited by: charlie d. ]
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Nel
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posted 07. April 2003 19:34
Charlie,
Replacing clonal selection system with an antibody administering i.v. is irrelevant. Invertebrates release substances that attract phagocytic cells and is also irrelevant.
With point 2, the same irrelevancy is at play. Yes, non-specific immune receptors are effective. A few specific antibodies are "not sufficient to make a difference". This would only be relevant if it can be shown that the shark system was ancestral to the mammalian system. IgM, as I said, in humans, are low affinity, but the secondary response, is highly specific and high affinity.
I don't see how Shark antibodies disprove the signle-epitope function of the immune system. The shark system is like a "one gene, one antibody" system and looks absolutely nothing like the mammalian system.
Secondly, Charlie d and Matt Inlay did indeed blunder, and the error is fatal with respect to innate receptors with single specificities. Behe stated that antibodies that bind to a particular epitope would be useless , or in his words, "not sufficient to make a difference". Inlay (and yourself) attempted to counter this argument by saying that innate receptors with single specificities are basically antibodies. Thus Behe is wrong, claims Inlay, we see organisms with few antibodies getting by just fine. But Inlay is wrong, the receptors he mentioned are generic binders. Behe's point still stands. I think this is a simple point to understand. Inlay's argument here critically depends on these receptors having single specificities, thats why he stated it this way. Otherwise the analogy to antibodies is quite irrelevant to Behe's point about IC and this system. With respect to this system, it is IC. And even the literature shows this.
With regard to point 5, which IC steps does the complement lack? Neither you nor Inlay say so. In the essay, he just complains about Behe not mentioning the function of complement and he describes a third complement system that basically acts as the classical pathway.
As far as I'm concerned, the alleged "dead horse" is still alive and kicking. Note that charlie fails to mention specifically (pun intended) what "twists" I took. That is because I didn't take any. As far as the rest of Charlie's assertions, one simply need to look up the literature I cite above, as recent as 2001, that shows data that is consistent with IC. This would require the Darwinist to "give up", once he realizes there are simply no precursors to the immune system.
[ 07. April 2003, 19:41: Message edited by: Nelson_Alonso ]
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charlie d.
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posted 07. April 2003 20:04
quote:
Nelson:
Note that charlie fails to mention specifically (pun intended) what "twists" I took.
Fair enough. I meant all the twists between this:
quote:
Charlie:
What would you define as the primary, original function of an antigen receptor molecule?
Nelson:
To recognize foreign substances.
and this: quote:
Nelson:
Here is my functional definition of effective antibodies with respect to immunity:
1. The ability to be specific
2. The ability to exhibit great diversity.
3. The ability to neutralize toxins
4. immobilization of microorganisms.
5. neutralization of viral activity
5. clumping together of microogranisms.
6. binding to soluble antigen for the formation of precipitates.
7. activating complement
8. Being able to cross the placenta from the mother to the fetus.
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gedanken
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posted 07. April 2003 20:26
I want to avoid all negative comments on this page one, to the degree possible, according to the rules.
Alonso, could you please tell us in detail what the "positive" evidence is for ID, as stated in your opening paragraph? (By that I mean evidence for ID, as opposed to evidence against evolutionary theory and observation.)
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yersinia
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posted 07. April 2003 21:55
Nelson, you can't just make up stuff as you go along in order to avoid admitting that you're wrong. E.g.:
quote:
I don't see how Shark antibodies disprove the signle-epitope function of the immune system.
They have a rearranging-antibody immune system without single-epitope antibodies. Therefore such systems are functional in direct contradiction to your assertion.
(And, apparently, mammalian rearranging antibodies have immune-relevant function even before they get mutated-and-selected to high specificity, another contradiction between you and the facts)
quote:
The shark system is like a "one gene, one antibody" system and looks absolutely nothing like the mammalian system.
????? C'mon, Nelson, sharks (and rays etc.) are well-known as the most basal group *with the rearranging vertebrate immune system*. Are you trying to tell us that the unevolvable boundary is *after* the sharks split off? Then you've already lost, as they already have recombinant immunity.
Regarding the complement system, you didn't actually read Inlay's article because you couldn't answer charlie d's question. There are plenty of invertebrates with only parts of the complement cascade. This is why Poenie (one of your quotes in the opening post was from him, you should add his name) admitted that this "IC" system had originated gradually.
There is much more, but we might as well do just a few things at a time.
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yersinia
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posted 07. April 2003 22:05
Yersinia's posturings deleted by Moderator.
[ 08. April 2003, 21:59: Message edited by: Moderator ]
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yersinia
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posted 07. April 2003 22:47
Nelson/Behe's single-specificity requirement for the precursor to rearranging antibodies is a red herring.
1. If general receptors are useful, and they are because many organisms have them and use them, then all we need to postulate is that rearranging began in a general receptor and resulted in some improvement of recognition of specific invaders.
2. Nelson for some reason thinks that the first rearranging receptor wouldn't produce enough "specific" antibodies to "make a difference". But if the RAG insertion occurred in some commonly used general innate receptor, then when the receptor gene was expressed, the mutant organism would have the same number of receptors as its parent, they would just be a bit more diverse. And we know that diversity of immune receptors is a good, selectable thing because we can observe direct evidence of selection for immune receptor diversity in many organisms today.
3. It bears pointing out that re-arranging ain't everything, and that many of Nelson's assertions along the lines of "pathogens would out-evolve innate receptors" are fallacious for some very important antigens.
E.g., bacterial flagellin:
quote:
Curr Top Microbiol Immunol 2002;270:93-108
Toll-like receptor-5 and the innate immune response to bacterial flagellin.
Smith KD, Ozinsky A.
Department of Pathology, University of Washington, Box 35610, 1959 NE Pacific Street, Seattle, WA 98195, USA.
The innate immune system identifies the presence of infection by detecting structures that are unique to microbes and that are not expressed in the host. The bacterial flagellum (Latin, a whip) confers motility, on a wide range of bacterial species. Vertebrates, plants, and invertebrates all have evolved flagellar recognition systems that are activated by flagellin, the major component of the bacterial flagellar filament. In mammals, flagellin is recognized by Toll-like receptor-5 and activates defense responses both systemically and at epithelial surfaces. Here, we review the role for Toll-like receptor-5 in mediating the mammalian innate immune response to flagellin, and how this provides for defense against infections caused by many different species of flagellated bacteria.
Trends Plant Sci 2002 Jun;7(6):251-6
Flagellin perception: a paradigm for innate immunity.
Gomez-Gomez L, Boller T.
Seccion de Biotecnologia, IDR, Campus Universitario s/n, E-02071 Albacete, Spain. mlgomez@idr-ab.uclm.es
There are surprising similarities between how animals and plants perceive pathogens. In animals, innate immunity is based on the recognition of pathogen-associated molecular patterns. This is mediated by the Toll-like receptor (TLR) family, which rapidly induce the innate immunity response, a first line of defence against infectious disease. Plants have highly sensitive perception systems for general elicitors and they respond to these stimuli with a defence response. One of these general elicitors is flagellin, the main component of the bacterial flagellum. Genetic analysis in Arabidopsis has shown that FLS2, which encodes a receptor-like kinase, is essential for flagellin perception. FLS2 shares homology with the TLR family, and TLR5 is responsible for flagellin perception in mammals.
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Nel
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posted 08. April 2003 17:51
Note in this post I reply to Ged, Yersinia, and Charlie
LOL Charlie. That is not "twisting". The basic function of an antigen receptor, is to respond to foreign substances. That's it in a nutshell. Which is why I do regard innate immunity as , immunity. My list describes what makes acquired immunity an effective defense against those same foreign substances for vertebrates. You had asked for such a list, when you made your own and inquired what I thought about it because you were "confused".
Since I don't want to make a short post I'll kill three birds with one stone.
Ged,
As I mentioned, the positive evidence for an ID argument is the fact that natural Darwinian processes wouldn't know, with antibody diversity for example, wouldn't have any selective advantage with just a few antibodies with single specificities (which is why Inlay asserted that innate receptors with single specificites are basically primitive acquired immunity). Since acquired immunity had to appear all at once, and it is extremely complex, I hypothesize that it was intelligently designed, it didn't evolve. I even offer a mechanism for one of the key machines of acquired immunity (the Rag machine), lateral gene transfer. The literature is consistent with this hypothesis when it mentions the "Big Bang" of acquired immunity.
Yersinia,
The fact that sharks don't have single-epitope antibodies supports my point. You don't see a few antibodies with single specificities because that is selectively disadvantages. That is what is IC about antibody-diversity. I didn't make any thing up at all. What did I make up?
What is relevant about immune relevant function before they get to high specificity? The fact that they do is what I'm pointing to.
As I stated sharks are only relevant if you can show that their immune system was the ancestral state to the mammalian state. Furthermore, shark antibodies are already arranged. It looks absolutely nothing like the mammalian system, in fact, the arrangement itself poses a problem for such a transition which I'll get to tomorrow (have only 10 minutes left here).
quote:
Regarding the complement system, you didn't actually read Inlay's article because you couldn't answer charlie d's question. There are plenty of invertebrates with only parts of the complement cascade. This is why Poenie (one of your quotes in the opening post was from him, you should add his name) admitted that this "IC" system had originated gradually.
Again, which "IC steps" were shown to evolve with regard to the complement system? As I showed with the complement cascade, each cascade still has switches, which is what Behe was pointing to that is IC about the complement cascade. In fact, all the cascades are analogous to eachother. Lastly, I don't think you ever answered me as to where Dr. Peonie stated that the complement cascade evolved gradually. You probably did asnwer me but I probably didn't get to it. But this is the best time to quote him as I couldn't find it. I do remember you saying something to the effect that you said something and "Dr. Peonie didn't reply". If that is what you are going to respond with, I gotta laugh.
Yersinia writes:
quote:
Matt Inlay's article "Evolving Immunity" showed that Behe's assertions about why the immune system couldn't evolve were wrong, and furthermore that there was a huge mass of literature on the topic of the evolution of the immune system, and indeed a whole field of research known as "evolutionary immunology".
Sorry to burst your bubble, however the literature doesn't describe in detail how the immune system evovled through natural selection and random mutation. Neither does Inlay, his story is so vague and undetailed, like most IC systems that Behe talks about. Furthermore Inlay has made quite a few mistakes which were crucial to his points, such as with TCR and innate receptors. Furthermore, the litereture shows a "Big Bang" that occured, where acquired immunity appeared abruptly. All of this is consistent with IC. Note Yersinia, has chosen to forgo quoting any article that shows the acquired immune system evolving step by step through random mutation and natural selection.
With respect to innate receptors, why do you keep bringing up the irrelevant point that innate receptors are useful? Heck, even ID theory would have a problem if innate receptors weren't useful. Why would the designer give invertebrates an immune system that didn't work?
The problem is getting from generic binders to specific binders. A few specific binders are useless to the immune system. All of my points regarding this was ignored:
quote:
A receptor with a single specificity can be bypassed or adapted to by a bacteria. There is also the problem of the loss of those receptors with single specificities through stochastic evolution. Which means if a pathogen whom that specific receptor was acting as an antibody for disappears from the population for a while, a mutation occurs where loss of that specied innate receptor or group of specified innate receptors are now gone, this is inherited in a population, the pathogen comes back, they all die.
With those organisms that just have innate receptors, or even one or two antibodies, are in an arms race that may be too much for them. Just as the Red Queen said, "Sometimes it takes all the running I can do to stay in the same place." At least thats Behe's point. I think thats why it's most parsimonous to say that it arrived in large vertebrates or at least was in wait for large vertebrates. Dr. Peonie makes a good point:They are just examples.
Again, if Yersinia would read my post and actually read the literature he references rather then just quote them as if they somehow contradict my post, he would realize how irrelevant those two papers are. As I already mentioned toll-like receptors are irrelevant to Behe's point, for example, TLR4 is generic, just like hemolin, just like scavenger.
Yersinia talks about the first Rag gene recombining innate receptors in a "mutant organism", but that won't do any good. Innate receptors are generic! All of the complexity of clonal selection and antibody generation in order to make a large repetoire of specific binders is completely ignored in this scenario.
Unfortunately, I have to go, but I'll be back tomorrow morning to flesh these responses out. But hopefully this will serve as an impetus for more relevant replies regarding the irreducible complexity of combinatorial immunity.
[ 09. April 2003, 19:43: Message edited by: Nelson_Alonso ]
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charlie d.
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posted 08. April 2003 18:09
quote:
That is not "twisting". The basic function of an antigen receptor, is to respond to foreign substances.
So, now, are you unequivocally and definitively stating (again), that this is the "basic, and therefore original function" of the adaptive immune system, that should be used in establishing its ICness? Or is this just a back-flip?
All I am saying is that, since a functional definition is supposedly essential for determining the ICness of a system, and despite your absolute certainty that the adaptive immune system is IC, it's been mighty difficult to pin down what definition you are actually using.
[ 08. April 2003, 18:25: Message edited by: charlie d. ]
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gedanken
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posted 08. April 2003 19:46
The thread A sequence of tests for IC contains a number of definitions of IC. Those definitions are labeled by very specific tags.
In addition there are "tests" that are in a logical form, which are supposd to be the basis for refining to a laboratory procedure or the like. Generally they are not narrowly focused, but even narrowly focused tests for IC would be welcome, so long as that thread did not devolve into a debate on the "IC" nature of some indivudual case. (I wanted such debates to proceed in respective threads, and the "tests" thread to study tests and definitions in generalized logical level for their generalized implications.)
So Alonso or others could point to the very specific definition and test he is using. And if it is not in that thread, he could add it. (But of course if having the definitions and tests stated clearly is disadvantageous to ID promoters, then they might choose not to do that. But others could go ahead and abstract the generalized "test" procedures that ID advocates appear to be using and then refer to those in individual threads like here -- referring to the exact labeled definition and test by the labeling system of that thread.)
Even if ID advocates won't put up precise definitions, others could do so and thus help improve the level of specificity in all questions of definitions and tests, such as is occurring in this thread.
[ 08. April 2003, 19:50: Message edited by: gedanken ]
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warren_bergerson
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posted 09. April 2003 07:37
Nelson should be complimented for suggesting a line of analysis which offers the potential for clarifying the relationship between ID and Darwinian theories. The impact of lateral gene transfer on genetic and evolutionary theories seems to be particularly interesting.
With respect to the species at that receiving end of a lateral gene transfer, the imported genetic material is the product of an ‘external genetic design process’. With respect to the receiving species, it does not matter whether the source of the received genetic material is an unrelated species, a genetic engineer, an alien or a supernatural being.
The existence of ‘externally designed genetic material’ raises important questions for neo-Darwinian genetic theory. Does neo-Darwinian genetic theory purport to explain genetic change resulting from external design processes? Does the theory ‘fit’ genetic changes produced by external design processes or are the results of external design processes incompatible or inconsistent with the theory?
A lateral gene transfer is logically equivalent to a wobble or inconsistency in the orbit of a planet. Does genetic theory ‘explain’ the observed wobble or does the wobble suggest the existence of an external factor impacting on genetic change?
Does genetic theory ‘predict’ what genetic changes can be produced by genetic change processes, or does genetic theory simply assert that ‘whatever happens is always compatible with, always explained by the theory. Genetic theory is predictive if it can and does predict what changes can be produced and predicts what genetic changes can not be produced. If genetic theory can not differentiate between possible and not possible, then it is a descriptive, non-predictive, and IMO, non-scientific theory. If genetic theory is predictive, then it is testable. If it is not predictive, it is not testable.
I can’t tell from what has been posted, what type of ID theory Nelson intends to propose. However, it would appear that a descriptive ID theory of the form "Genetic change can be produced by ID’ is logically equivalent to a descriptive neo-Darwinian theory of the form "Genetic change can be produced by RM&NS".
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Nel
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posted 09. April 2003 17:06
I wrote:
quote:
That is not "twisting". The basic function of an antigen receptor, is to respond to foreign substances.
Charlie replied:
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So, now, are you unequivocally and definitively stating (again), that this is the "basic, and therefore original function" of the adaptive immune system, that should be used in establishing its ICness? Or is this just a back-flip?
Note the addition of the words (which I bolded) that does not appear in any of my posts. You seem to think that I stated that antigen receptors are IC. I want to ask you to quote me specifically where I claimed that receptors are IC and that the original, basic function of this IC system is that it responds to foreign substances, where I then subsequently changed the definition to the 8 characteristics I think describe antibodies of the combinatorial immunity (which can be essentially grouped into the phrase "response to foreign substances" with respect to acquired immunity).
While I'm waiting for that response, I'll cut and paste the definition I had pinned down weeks ago in two threads for one of the IC systems within combinatorial immunity that I started with: antibody-diversity, which lead you to erroneously (again and again) think that I kept changing my definitions.
quote:
I think Behe's point here is that there is a dangerous gap between the jump from innate immunity to acquired immunity, acquired immunity is largely successful because it can generate specificity for any kind of foreign substance. Innate immunity cannot. And then there's the fact that if innate immunity consisted of receptors with single specificities, then the likelihood of a foreign substance being recognized diminishes. Even if there are some innate receptors or something like them, with single specificities, a handful of them wouldn't be enough. Which is why Behe says that a system with only a few antibodies are "not sufficient to make a difference".
Note I have cut and pasted this quite a few times and it keeps getting ignored. Note also the date for this quote: posted 16. March 2003 21:57. Note also this was after I defined what an antigen receptor is, and before I listed the 8 characteristics of antibodies. Perhaps I should quote Behe here which mimics what I said.
quote:
"The problem of diversity runs headlong into the requirement for minimal function. A primitive system with only one or a few antibody molecules would be like the propeller turning at one revolution per day: not sufficient to make a difference... Because the likelihood is so small for the shape of one antibody being complementary to the shape of a threatening bacterium -- perhaps one in a hundred thousand or so -- any animal that spent energy making five or ten antibody genes would be wasting resources..." (Page 130-1).
Note also this was quoted in Inlay's article, which is where I am quoting it from. Inlay then goes on to say:
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Behe is totally wrong to assert that receptors with single specificities are useless to the immune system.
http://makeashorterlink.com/?A22E21724
So if he can find a few receptors with single specificities that act as an effective immune system, he would have effectively found a "primitive system with only one or a few antibody molecules" as Behe stated it.
But as I keep saying, Inlay is totally wrong to think that innate receptors with single specificities are useful to the immune system. Innate receptors with single specificities are useless to the immune system, for the reasons I already discussed. The receptors he mentions are not specific, they are generic, which is why they are effective and useful.
Which is why I keep yawning when both Nic (Yersinia) and yourself keep emphasizing how innnate immunity is effective. I simply nod, and think "so what?".
[ 09. April 2003, 17:43: Message edited by: Nelson_Alonso ]
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Nel
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posted 09. April 2003 17:17
Ged,
As an aside, this weekend, I plan to look over all the threads I participated in in order to get to all the posts I haven't replied to yet. I'm pretty sure I missed quite a few. So expect quite a few posts in your own thread in which I will answer your questions regarding IC (I will also discuss there the quesitons you posed to me in the Organisms GA thread as well concerning the bacterial flagellum).
Now, let me make clear that I think that your thread "sequence of tests for IC" is irrelevant. For example, one of your sequence tests was completely off the mark, second knockouts don't restore function, there is simply no biological example of such a thing ( I realize Rex talked about supressors but that has absolultey nothing to do with knocking out second components of the system and getting the function back, but I digress).
Secondly I keep challenging you to randomly pick any definition of IC that you see out there defined by ID theorists (Dembski, Behe) and show that it somehow does not apply to any of the systems I discuss (ATP synthase; combinatorial immunity - antibody diversity, clonal selection, complement cascade; bacterial flagellum). You have never accepted this challenge. The reason why I am challenging you to do this is because, as I keep saying, I think that all the definitions for IC are functionally equivalent. Even the very differently worded evolutionary definition.
Now, that I do not label my definitions is not necessarily because doing so is disadvantageous to me. In fact, I'm giving you,the ID critic, a huge advantage in that you can pick the definition and test you think contradicts my application of IC in this thread and show specifically how it is not IC, and you have a refutation of OP, and without having to know a thing about immunity to boot.
Another aside, I want to make clear that I don't think that the IC definition expressed in 1996 must be immutable in order for ID to be coherent. Definitions are changed in science all the time to reflect new ideas as a consequence of more research and new data. Definitions are often made more precise (or "salvaged" as Dembski referrs to it) and this is a good trend. This is why when someone usually asks me to define IC I usually give them Dembski's definition, because Behe's definition was meant for a wider audience and as a consequence is susceptible to misinterpretation when it is taken out of context. On the other hand, it is impossible to take Dembski's precise definition out of context. And more likely, the definition will undergo more precision and revision as time passes on to reflect and nail down what the issue is at stake. An evolutionary definition or one whose focus is off the parts is probably forthcomming and that will likely reflect the original definition even though it will most likely be more precise. Of course I"m just speculating here from what I've read about IC from prominent IDers. One day, it may be possible that the definition for IC will be completely different from the original version, perhaps nothing like it, perhaps it will still reflect the point of IC in that it is a problem for the Darwinian mechanism and an indication that intelligence is at work behind the IC system, but the definition itself may reflect different aspects of a particular biological feature, but this hasn't happened yet.
It is simply my observation that the definitions are simply not different, no matter how many "sequence tests" you come up with, no matter how precise you get with the language. This is simply a matter of fact and not a matter of Beheian inerrancy where everything he said is immutable, the issue comes down to, Behe's definition has simply stood the test of time.
[ 09. April 2003, 17:39: Message edited by: Nelson_Alonso ]
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charlie d.
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posted 09. April 2003 18:26
Nelson: thanks for your answer. Alas, not only you forgot to clearly tell us what the "core, and therefore original function" of the IC system actually is, but now also seem to have started equivocating about what the system itself is (the receptor? somatic recombination? adaptive immunity?).
Please, to facilitate discussion, just write it down once and for all:
- Purported IC system:(eg, a high affinity/high specificity antigen receptor system)
- Core, and therefore original function: (eg: high specificity recognition and elimination of antigens)
- Components: (eg, antigen receptor gene segments, RSSs, RAGs)
Thanks
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