Behe versus ribonuclease; the origin and evolution of protein-protein binding sites

Posted 13 April 2008 by Ian Musgrave

The core concept of Dr. Michael Behe’s recent book “The Edge of Evolution” (Behe, 2007) is that protein-protein binding sites are extremely unlikely to have developed by natural means, and therefore were designed by unknown intelligent agents. There is a lot of interest in this concept, as the tag cloud at PT indicates. A recent paper (Grueninger et al., 2008) on human design of binding sites undermines some of his key assumptions, but what is more interesting is an old paper cited in Grueninger that shows researchers have known for some time that evolution of protein-protein binding sites is not as difficult as Behe makes out. Indeed, his very premise was invalid from the beginning. Compared to his central image of “Darwin’s Black Box”, the mousetrap, “hard to evolve protein-protein binding” is a far more abstract and much less memorable idea. No matter how deeply misleading the image is a mousetrap at least is something concrete; you can even hold one in your hand. Submicroscopic things that blobbily stick together just don’t catch the imagination in the same way. This may explain why “Edge of Evolution” has had less impact than “Darwin’s Black Box”. However, to understand the importance of Behe’s claim, consider that many of the proteins in the cell strongly bind to other proteins in order to function. Such protein complexes can range from the simple systems like haemoglobin, the oxygen carrying protein of the body which is made of two separate proteins bound together, to more complex systems like the proteasome, a barrel–shaped complex of 28 subunits which is the garbage bin of the cell that disposes of cellular proteins past their use-by date (Gilles et al., 2003, Valas & Bourne 2008). Proteins in such complexes generally bind through specific protein-binding sites, which are complementary areas of the two proteins surfaces. Typically a surface loop on one protein (a “bump”) will fit into a corresponding pocket on another protein (a “hole”), so that the proteins fit together like a key fitting into a lock (see figure). Of course, in nature things are rarely this simple. Amino acids can be neutral, negatively charged, positively charged or slightly “oily”. Usually the amino acids of the bump and hole will have complementary charges or “oiliness” as well. On the other hand, the “Lock and Key” image is far too rigid. Proteins are flexible, and will wobble, flex and change shape, so they represent floppy locks and keys, in which a range of shapes may fit. Proteins bind together like a "lock and key" with "bumps" on one molecule matching "holes on the other, electrical charge and oiliness are also factors. Behe’s basic argument in “EoE” is that protein-protein binding sites contain many interacting amino acids, and that all (or a large majority) of these amino acids must be in place simultaneously for strong, biologically meaningful, protein-protein binding to occur. Note the word simultaneously. As with the “irreducibly complex” mousetrap model, Behe assumes that there is no possible one-mutation-at-a-time path to these binding sites. He doesn’t even mention the possibility in his discussion of binding sites (see the “two-binding site rule”). This is a mirror image version of the Behe & Snoke paper (Behe & Snoke, 2004), that assumed that any binding site could only be reached by multiple neutral mutations, without any role of natural selection. While in the Behe and Snoke paper they calculate the probability of multiple, sequential, neutral mutations in specific locations, in “EoE” Behe calculates the probability of two simultaneous mutations in specific locations. Human Growth Factor receptor (pink) binding to its ligand, Human growth hormone (white). The ligand binding pocket of the Human Growth Factor receptor is shown in orange, but only two amino acids are responsible for the vast majority of the binding (shown in blue). Alternate amino acids can be inserted and high affinity binding still occurs. Unlike Behe implies, you don't need enormous many amino acids in particular positions to form a binding site. Behe claims that for even a simple binding site composed of two amino acids in specific locations that you would need a population of around 10²⁰ organisms to evolve it. Since for large organisms, such as humans, whales, wildebeests and wolverines, this is many orders of magnitude larger than the total population of these organisms over their entire history on this planet, Behe claims we cannot have developed many protein-protein binding sites by natural means. Yet our cells have over 10,000 protein-protein binding sites! Thus, Behe says, multisubunit protein complexes must be the work of a (unknown) designer. Let’s just stand back for a moment and quickly summarise Behe’s claims:
1) Protein-protein binding sites must be produced by multiple, simultaneous mutations in a specific sequence.
2) There are lots and lots of protein-protein binding sites in modern organisms, far more than could be produced during the lifetime of any given species. To take the second claim first, note the slight of hand involved. Humans do have lots of protein-protein binding sites, but we didn’t develop them de novo. The vast majority we inherited from our common ancestor with the chimpanzees. That hominid in turn inherited most of its protein binding sites from its ancestors, and so on. Indeed, the majority of the most impressive protein-protein complexes evolved in single celled organisms over hundreds of millions, if not billions, of years. The populations of these organisms far exceed the measly 10²⁰ that Behe invokes. But reading “EoE” Behe certainly gives the impression that all these protein-protein complexes must have evolved relatively recently, without a deep history. Take the proteasome, it didn’t evolve in some slow reproducing, lumbering multicellular organism, it evolved in bacteria back in the deep Precambrian. For someone who claims that he accepts evolution and natural selection, Behe certainly ignores it when considering protein-protein binding. He also ignores a very important aspect of the evolution of binding sites, exemplified by the proteasome. I’ll amplify this later, but for the moment, hold this thought, Behe ignores known details of protein evolution. Now, after that roundabout introduction, I’ll return to the first point. Behe implicitly assumes that there is no simple, step by step selectable path to strong protein-protein binding (he also implicitly assumes that there is no step by step path to any multiprotein complex). But is his assumption true? In the paper I introduced at the beginning of this essay, Grueninger et al. were trying to engineer binding sites into proteins. They were able to produce strong protein-protein binding in many cases with a single mutation. Not only that, the proteins produced multimers of a variety of sizes. Let’s repeat that again, a single mutation produced strong protein-protein binding which resulted in protein complexes. And the researchers hadn’t exhaustively tested all possible mutations and binding sites. Now, these complexes were composed of identical proteins, but this is actually quite important and I will elaborate on this momentarily. But buried away in the references was a paper that was even more illuminating. This paper was looking at the basis of the binding of bovine seminal ribonuclease. Ribonuclease is an enzyme that, as its name suggests, breaks down ribonucleaic acid. These enzymes are typically monomers, but bovine seminal ribonculease is a modified duplicate of standard ribonuclease which is a dimer. The question that researchers were interested in was which mutations were responsible for binding. At stake was a particular model of how proteins bind to each other. To explain this, I have to briefly diverge into a discussion of protein folding. When proteins are synthesized in a cell, they have to fold up into their final, three dimensional shapes. In this process, loops on the protein chain fit into pockets in the protein chain. Sound familiar? It’s the same process the produces protein-protein binding. One of the simplest ways for two proteins to bind to each other is if the loop of one binds into the pocket of the other (see the diagram). You can see that it would be very simple to set this up. In the end the researchers found there were multiple ways to get ribonulcease to dimerise. One mutation was all it took. So we have evidence that in nature, single mutations are all it takes to produce important protein-protein complexes. And we have had this evidence for sometime. Why didn’t Behe address this? Evolution of homodimer binding, there are two rapid paths to forming homodimers, using internal structures of the protein. Both paths appear to be used, and it takes only a single mutation to generate strong homodimer binding. Diagram taken from Canals et al., 2001. We can ask how relevant these results are. Are dimers and multimers of the same protein at all useful? Certainly the bovine seminal ribonuclease is. And indeed, dimers and multimers of the same protein play very important roles. For example, the nicotinic receptor composed solely of five α7 subunits is important in brain function, and there are many similar examples. As well, these homomultimers are raw material for more complex systems. Duplication and subsequent mutation of the nicotinic a subunit produced beta subunits, in the same way that monomeric haemoglobin became a tetramer of α and β subunits (something Behe accepts). The key issue here is that a mutant α subunit that becomes a β subunit retains the protein-protein binding site, it doesn’t have to reinvent the whole thing again. And the whole process can be repeated several times. There are several crucial nicotinic receptors composed of variant αb complexes. Subsequent duplication and divergence produced the complex αβγδ nicotinic receptor of the skeletal muscle. Duplication of the genes for homomultimeric proteins, with subsequent mutation and divergence, can generate large families of interacting proteins without having to generate new binding sites. This process can produce significant complexity, remember the 28 subunit proteasome? Well, in the many primitive organisms, it is constructed solely out a αβ dimer. The dimer is the result of duplication of a simple monomer (and many eubacteria have a simple 12 subunit proteasome composed of a simple monomer which appears ancestral to the dimeric proteasome (Gilles et al, 2003, Valas & Bourne 2008). Subsequent duplication and divergence of the dimer genes produced the 28 subunits that are found in vertebrates, but it all started with a very simple multimer. Again, although Behe says he accepts evolution and natural selection, he ignores the role of evolution in generating structures such as the nicotinic acetylcholine receptor family, the sodium channel family, the potassium channel family, the proteasome, GABA receptors, AAA+ ATPases, NMDA receptors, glycine receptors, histamine H3 receptors … you get the idea. Vertebrate proteasomes are complex barrel like structure of 28 subunits. These evolved by duplication and divergence of a structure made of simple αβ dimers. The α subunit (yellow) itself is a duplicate of the β subunit (red) . The E. coli proteasome is made of a single subunit (red), which shares a common ancestor with the β subunit. Image from Groll et al., 2003 So, a large proportion of protein-protein binding is due to structures that started out as homomultimers, which we have seen can evolve very easily indeed. That’s all very well, but not all protein complexes began as homomultimers. For example, in the voltage-operated calcium channel family each channel is a complex of unrelated proteins. Now, one of Behe’s assumptions is that proteins in protein-protein complexes have no function unless they are in a complex, but in fact this is often not the case. The α subunit of the voltage operated calcium channel is in fact a fully functioning ion channel. The α subunit complexed with either the β subunit alone, or the β and γ subunits modify the characteristics of ion flow through the channel. Again, multiple forms of voltage gated calcium channels are formed by duplication and divergence of the subunits. Again, there is no need to develop entirely new binding sites, these are carried over with the duplicated proteins, and again there are multiple classes of proteins that follow this pattern. For example the NADPH oxidase family are diverged duplicates, which exists as simpler systems in simpler organisms. Even in these kinds of heteromultimeric complexes, some of the elements will be internal duplicates as well, making things simpler. The scope of this inheritance of binding sites can be illustrated with the G-protein coupled receptor family. The receptor protein is in a complex with the eponymous G-protein [1], through which it signals. The repertoire of vertebrate G-protein coupled receptors are modified duplicates of the original G-protein coupled receptor in single celled organisms. How big is that repertoire? In vertebrates there are around 500 G-protein coupled receptors, that represents a big chunk of the approximately 10,000 protein-protein binding sites that Behe cites that don’t have to be evolved from scratch. Now consider that most protein complexes are parts of families, even before we consider the huge families of protein complexes that evolved from homomultimers, and Behe’s big numbers begin to melt away like snow at Arakarula[2]. We have up to now considering simple point mutations. But there is another way proteins can gain binding sites. That is through gene fusion or crossover, where segments of genes containing binding sites can be swapped into other genes. Indeed, in the protein kinases, new targeting binding sites have been produced in just this way. Duplication, divergence, crossover, fusion and inheritance; once again, Behe is unacquainted with the evolutionary history of the systems he claims to describe. However, while there is lots of experimental evidence that single mutations can easily produce high affinity homodimers and homomultimers (which then, by duplication and divergence, result in the protein complexes that we see today), can such simple, one amino acid mutations produce binding between entirely different proteins (say the α and β subunits of the voltage gated calcium channels)? The answer is yes. Once again, we turn to bovine seminal ribonuclease. The simple mutation that made it dimerise has also lead it to bind to a variety of other, unrelated proteins (without any harm to cows). This emphasises the messy, contingent nature of biology, and also illustrates that protein-protein binding is a lot easier to evolve than Behe claims. Summary Behe claims that there are a huge number of protein-protein binding sites, and that even one protein-protein binding site is extraordinarily difficult to evolve. However Behe greatly overestimates the difficulty of developing a binding site, ignores the fact that the majority of 10,000 binding sites in modern vertebrates are duplicate copies of each other, with there being only a much smaller number of basic binding motifs and ignores the fact that most of these basic binding motifs were developed in rapidly dividing single celled organisms with very large populations. Far from protein-protein binding pointing to an unknown designer, protein binding sites point directly to descent with modification and the “tinkering” of natural selection. [1] Strictly speaking, G-proteins bind to the G-protein-coupled receptors only when the receptors are activated, rather than permanently, as in voltage gated calcium channels. However, G-protein receptor binding involves the same issues of selective interaction of “bumps” and “holes” as with all other protein complexes. [2] Arkarula in the Flinders Ranges is on the edge of the great Australian Desert, and boy, is it hot!

Behe M. “The Edge of Evolution: The Search for the Limits of Darwinism”. Free Press, New York. 2007, pp. 135-147.

Behe MJ, Snoke DW. Simulating evolution by gene duplication of protein features that require multiple amino acid residues. Protein Sci. 2004 Oct;13(10):2651-64. Epub 2004 Aug 31.

Gille C, Goede A, Schlöetelburg C, Preissner R, Kloetzel PM, Göbel UB, Frömmel C.A comprehensive view on proteasomal sequences: implications for the evolution of the proteasome. J Mol Biol. 2003 Mar 7;326(5):1437-48.

Groll M, Clausen T. Molecular shredders: how proteasomes fulfill their role. Curr Opin Struct Biol. 2003 Dec;13(6):665-73.

Grueninger D, Treiber N, Ziegler MO, Koetter JW, Schulze MS, Schulz GE. Designed protein-protein association. Science. 2008; 319:206-209.

Canals A, Pous J, Guasch A, Benito A, Ribó M, Vilanova M, Coll M. The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization. Structure. 2001; 9:967-976

Ciglic MI, Jackson PJ, Raillard SA, Haugg M, Jermann TM, Opitz JG, Trabesinger-Rüf N, Benner SA. Origin of dimeric structure in the ribonuclease superfamily. Biochemistry. 1998; 37:4008-4022.

Valas RE, Bourne PE.Rethinking Proteasome Evolution: Two Novel Bacterial Proteasomes. J Mol Evol. 2008 Apr 4; [Epub ahead of print]

52 Comments

sparc · 13 April 2008

Did I miss this post or went something wrong with the date?

Ian Musgrave · 13 April 2008

No, something was wrong with the date. Stupid Movable type doesn't update the date when you have edited something over a couple of days.

David Stanton · 13 April 2008

So, for once I agree with Behe. I do not believe that it is possible for thousands of protein binding sites to arise simultaneously. Wait ... wasn't that the ID poof hypothesis? Why would this guy think that disproving his own hyothesis would somehow disprove evolution?

Behe has certainly heard the argument before. He certainly knows that he is ignoring all of modern biology when he makes his nonsensical claims. It has been pointed out to him so many times that by now he must surely know that hs is being deliberately deciteful.

What good is having a PhD if you don't use it to study the actual science? Why did he need to get a degree in order to ignore all of the scientific literature? Did he take the same approach in his previous career, or did he just adopt this strategy when he sold out to the ID nonsense? This tactic is very telling. If the only way that you can find to discredit science is to misrepresent it, on one is going to be fooled for a minute, unless they want to be.

Oh well, at least when he testifies under oath he always makes the evolution side look good. As long as he continues to ignore all of the evidence, the only thing he can be an expert in is his own delusions. I can't wait until the defense attorney in the California case puts this new stack of papers in front of him.

JGB · 13 April 2008

I'm not sure if anyone has pointed this out before, but there is a terrible math problem with the conception of the evolution of protein binding sites as requiring a pair of simultaneous mutations. He basically is trying to "model" the problem is if it took two unlikely events, so you simply multiply two small probabilities. Given the diversity of interactions that can lead to affinity the most accurate way is not by asking what are the odds of rolling double six. It is much more accurate to look at it as given the identity of this site, what are the odds of getting a favorable interaction at this other site. This is much more analogous to asking what are the odds of getting two numbers the same when you roll two dice (i.e. 1 out of 6 instead of 1 out of 36). As alluded to above given natural selections opportunistic nature as it were it is not even accurate to restrict yourself to a single site looking for a match in most cases. Similarly I would venture that in many cases restricting yourself to a single protein as being the only one that could possibly evolve the protein binding properties in question would also be fallacious.

Joel · 13 April 2008

Great post! Although all the ideas you call upon in your essay are familiar, you have a gift for putting them together in an interesting and compelling way. Thanks!

Venus Mousetrap · 13 April 2008

Behe is a liar.

There isn't really any other way to put it. It's been ten years since DBB. Ten years since he argued against a strawman kiddie version of evolution with all the evolutionary power removed from it. And here he's back with the same argument again, like it never happened. Like Dembski, he's only gonna do enough work to give the fundies stuff to quote, and go LA-LA-LA when anyone notes his deliberate mistakes.

I mean, I can understand what's wrong with Behe claiming that evolution only works by addition (it doesn't) or Dembski claiming that all fitness functions are equally likely (they're not), and I'm not a biologist or a mathematician. I have nowhere close to their education, and yet I can sit here and watch them pretend nothing is wrong, and know that they are lying. It's disgusting.

Flint · 13 April 2008

...and yet I can sit here and watch them pretend nothing is wrong, and know that they are lying.

Well, to give them as much credit as possible, they are attempting to solve a very difficult problem: How can the evidence be interpreted in such a way as to require their god? Given that the evidence is entirely consistent with our species, like every other, being a contingent and temporary accidental outcropping of a continuous and indifferent set of natural feedback processes, how CAN we "discover" that goddidit, and we are the exalted purpose of creation after all? For folks like Behe (as opposed to Miller or Collins), merely projecting divine purpose onto a process that needs none just doesn't satisfy. They are desperate to establish that they couldn't have happened without the clear and necessary machinations of their god. Fortunately for Behe et. al, they have at their disposal the Religious Method to establishing Truth: just lie. If they gussie up their lies with enough scientistical-sounding jargon, god will be fooled. They KNOW god is fooled - He TELLS them so. Can't get better ratification than that!

Infidel Michael · 13 April 2008

Flint: .. they are attempting to solve a very difficult problem: How can the evidence be interpreted in such a way as to require their god?

I don't think it is a very difficult problem (for them). Look, it is enough to take a quote from this article:

Grueninger et al. were trying to engineer binding sites into proteins. They were able to produce strong protein-protein binding in many cases with a single mutation.

ID comment: See?! They've designed these mutations and they tell us it somehow proves evolution? That's ridiculous! Only what they've shown is this process required intelligence.

---

Of course this kind of argument is stupid and misses the whole point, but for the creationist audience this is an elegant rebuttal. It is so easy for them, because they don't need to understand the biochemistry behind the experiment, all they have to know is there was SOMEBODY involved in this process. They'll dismiss the whole scientific work with god-did-it-the-similar-way conclusion.

Flint · 13 April 2008

Of course this kind of argument is stupid and misses the whole point, but for the creationist audience this is an elegant rebuttal. It is so easy for them, because they don’t need to understand the biochemistry behind the experiment, all they have to know is there was SOMEBODY involved in this process.

I really must disagree. Behe isn't a charlatan, he is a believer. I imagine he knows that there are logical issues with his arguments, and that his model doesn't fit the evidence very well. But the fact that goddidit is simply not open either to question or to self-serving rationalizations like Collins or Miller use. Behe knows that somehow, his god reached down and diddled directly with the raw materials. He can leave for later just exactly what process his god used; for now it's necessary to demonstrate that without the directed, purposeful interference of Behe's god, the process simply could not have happened. So as I see it Behe and his crowd don't really dismiss the scientific work, but they know that it is based on false assumptions. It MUST be, since it purports to show how biology works despite omitting Behe's god's immediate participation. And this means it's WRONG. It HAS to be wrong. As I said, it's a hard problem. It's hard because Behe is sincere. I think Behe is sometimes exasperated that his god has chosen to stay so well-hidden as to totally fool every biologist who doesn't areadly know the Truth before he starts. How frustrating it must be that the data are right THERE, but you need to be born again in Jeezus before Behe's god will make it visible to you.

PvM · 13 April 2008

Ian Musgrave pointed out elsewhere the 'core concept' --The core concept of Dr. Michael Behe’s recent book “The Edge of Evolution” (Behe, 2007) is that protein-protein binding sites are extremely unlikely to have developed by natural means, and therefore were designed by unknown intelligent agents.--

Thirdly, Behe claims zero new protein-protein binding sites in a population of 10^20 viruses over 60 years (EoE figure 7.4 page 144 and page 143). In fact, in less than 10 years, HIV evolved two protein-protein binding sites that lead to the formation of a functional protein-complex in a virus population of much less than 10^20, as this happened in the early stages of the disease, when the viral population was somewhere near 10^12 to 10^14, this strikes against Behe's population size requirements (the effective population size was probably even smaller).
— Ian Musgrave

slang · 13 April 2008

So next trial it won't be a stack of books and papers but just 2 papers that will demolish his testimony. Things are looking up!

Flint · 13 April 2008

In fact, in less than 10 years, HIV evolved two protein-protein binding sites that lead to the formation of a functional protein-complex in a virus population of much less than 10^20, as this happened in the early stages of the disease, when the viral population was somewhere near 10^12 to 10^14

From which Behe can certainly conclude that his god was at work. Certainly a coincidence of that magnitude is so obviously beyond the sort of random chance that entirely explains evolution, that only the veriest dunce could misunderstand Behe's god's divine hand at work, and only the blindest could deny it. Seems to me we have a very stout philosophical impasse here. Behe's hypothesis is that IF we can find such sites occurring this quickly, within this small a population, THEN his god is ipso facto responsible. QED. If Ian's hypothesis is that coincidences of this magnitude are natural regardless of the odds against them, then what Ian has done is ruled Behe's god out a priori; and there is then NO WAY Behe's god can make itself manifest. And we're back to the case where we have a no-doubt-about-it bonafide miracle right here in front of us. If science refuses to recognize it as such, then science can no longer claim to be neutral with respect to Behe's god. Science has taken the actively atheistic position that divine miracles MUST be interpreted as prohibitively unlikely, perhaps essentially impossible, as-yet-unexplained natural events. Which isn't very damn neutral. If I were Behe, I'd be willing to point directly to Ian's data and swear on a stack of bibles that we are witnessing god at work. Scientists have been begging for a genuine illustration, and here it is! NOW we see the scientists grabbing those goalposts and heading for Pluto!

raven · 13 April 2008

Behe confused: –The core concept of Dr. Michael Behe’s recent book “The Edge of Evolution” (Behe, 2007) is that protein-protein binding sites are extremely unlikely to have developed by natural means, and therefore were designed by unknown intelligent agents.–

That is odd. I evolve protein- protein binding sites all the time. So does everyone else and the cats or they are dead. This is the whole basis of adaptive immune systems, B and T cells. Gee, unknown intelligent agents floating around in my blood stream. Who knew and when?

Chris Lawson · 13 April 2008

Flint,

I agree that Behe is sincere in his *beliefs* (but then, who isn't?), but I disagree that he's sincere about the arguments he puts forwards. His arguments and evidence have been shown over and over again to be wrong. Yet he keeps putting them forward. After being demolished in Dover, you'd think that Behe would have read some of that stack of papers, but judging by his recent statements, apparently not. Even when he has engaged in direct communication with Ian Musgrave about his mistakes about malaria, he only made superficial concessions without ever conceding that the errors in the evidence were not trivial, they completely blew his conclusion. So, sorry, I could agree with your assessment back when Behe wrote Darwin's Black Box. That book could have been the result of a sincere effort by a poorly-informed and blinkered writer. But now his work can only be the result of a writer who is willfully ignoring the evidence against him and sees nothing wrong with disseminating misinformation.

Behe's Backer · 13 April 2008

Your disagreement isn't with Behe, it's with Galileo, Newton, Einstein - possibly with Darwin, himself, and certainly with mathematics, physics, and reason. It's also a disagreement with the man in the street. Every time this brand of 'Evolution' comes out with this self-evident impossibility, the people at AIG rub their hands together.

Mainstream scientists almost to a man have long accepted the findings of geology - an unfolding/unrolling of living forms, over time. I suspect most scientists, just quietly, have left it at that.

We have had the junk yard converting to a cadillac by blind chance, so repeatedly, I won't belabour anyone by pursuing it. But since we here claim the technical truth for evolution, and since there was a sequential unrolling of species, let's stand a few facts up and test theories. Before we start, a note on the quite professional and totally relevant presentation at the head of this page: it tells us that changes can, at least theoretically, occur in the incredibly sophisticated information carriers/controls within cells. What it conveniently neglects to mention, are the remarkable recent advances in nanotechnology, quantum physics, quantum computation, etc., especially the hints that are coming through, of the possibilities in relation to complex organic molecules. It turns out that dull old carbon, is anything but dull, when you get down to the atomic level. Every technical fact presented above, testifies in some way to information technology; and the information technology - a natural phenomenon - points the way to overcoming the entropy hurdle and to an explanation of the unfolding of life within the parameters set by physical chemistry.

Darwin & co. championed selective breeding in response to environment. Owen and many others saw purposeful pre-programming as the governing factor in evolution. (Owen coined the term, LAW OF PROGRESSION. He mentioned the Deity: his theory stands, without overt reference to religion.) Which of these two proposals - chance selective breeding on the one hand, and information- driven pathways on the other, is supported by the following?

Arrival of gymnosperms and other vegetation some hundreds of millions of years ago, giving fossil fuels.

Arrival of flowering plants less than 100 mil. yrs ago - many species even more recent - hence, pastures, edible foods etc..

Manifestation of domestic animals mostly immediately prior to Man. Animals such as horses and dogs, seemingly made for man.

Series of theoretically genetically distinct species in the geologic column - hence, a conduit down which life was passed, right back to the first in the series.

Information technology devices in every cell, theoretically capable of scanning in environmentally relevant information and of working in concert with (presumably quantum category) signals permeating the biosphere, to trigger species transformation and re-programming.

Discovery that 'toolkits' for 'building' organic structures in future species, were present in other species long before the 'building' was triggered. (E.g, HOX genes in paddlefish, seemingly waiting to be activated by some future trigger. See SCIENCEDAILY on this topic.)

Perhaps some basic analytical investigation is appropriate?

Flint · 13 April 2008

Chris:

I suspect we have a misunderstanding here about what "sincerity" means in a religious context. What I intend to mean is, a plain flat psychological inability to set aside non-negotiable, a priori religious preconceptions. Maybe "deluded beyond redemption" would be a better term than "sincere"?

I read the Dover testimony carefully, and Behe was NOT trying to say that the stack of papers on his lap was relevant research he hadn't bothered to look at. He was trying to say that he KNEW it couldn't be relevant to his religious concerns, because he knows that his religious concerns cannot be researched. One either accepts that goddidit, or one needs to return to church and start praying harder.

Behe understands that if you do not start with religious conclusions, you will not reach religious conclusions. And that if you impose religious conclusions onto your data, why, there they are, right in the data! His data aren't "wrong" and his arguments are sincere, provided you know what you're looking for and are determined to find it, regardless of how you must interpret the data to do so.

raven:

Yes, I think you got it (perhaps you don't realize it). The immune system demonstrates the Hand Of God at work in real time, in each of us, every day. Certainly immune responses are compatible with magical explanations (what isn't?), and you can't prove it's NOT magic. You can only show that the system is also compatible with an atheistic model which might be far more useful for medical purposes, but that doesn't make it RIGHT.

Flint · 13 April 2008

Backer:

You make two arguments here. One is what I've also been saying - that NO natural phenomenon can, in principle, be incompatible with a magical explanation. No question about it, natural feedback processes continue to produce Cadillacs with thumping regularity, needing only our opportunistic ability to exploit what's available us to to be completely divine (though Cadillacs have suffered serious reliability issues...)

The second argument you make is straight post hoc ergo propter hoc, and you seem to have this one mastered. You repeat as many times as you see fit, that if X happened, therefore X was supposed to happen. Who could possibly deny it? Granted, it's a bit weak on the predictive end, needing as it does to wait for something to happen before we can adopt it to the purpose it "must have been meant for". But other than that, well done indeed!

Venus Mousetrap · 13 April 2008

Behe's Backer : Darwin & co. championed selective breeding in response to environment. Owen and many others saw purposeful pre-programming as the governing factor in evolution. (Owen coined the term, LAW OF PROGRESSION. He mentioned the Deity: his theory stands, without overt reference to religion.) Which of these two proposals - chance selective breeding on the one hand, and information- driven pathways on the other, is supported by the following? Arrival of gymnosperms and other vegetation some hundreds of millions of years ago, giving fossil fuels.

Evolution, since the evidence shows that however this happened, gradual evolution was the mechanism. are you going to claim support for an intelligent fairy every time something seems convenient? In that case, you could ask the chap why three quarters of our planet is uninhabitable by humans, and why we're out in the sticks of the galaxy where stars are trillions of miles away. Or is it only the positive hits that count?

Arrival of flowering plants less than 100 mil. yrs ago - many species even more recent - hence, pastures, edible foods etc..

You realise, don't you, that if we didn't have pastures, we would have something else? Edible food did not arrive with the flowering plants. Again, it astonishes me that you're swung by such flimsy evidence. If glowing spike-vines had appeared 100 million years ago instead of flowers, you'd be making this same argument, which should be enough to show you it's wrong.

Manifestation of domestic animals mostly immediately prior to Man. Animals such as horses and dogs, seemingly made for man.

Um... clearly you haven't heard of domestication, which is the process which humans used to get these animals. Funnily enough, the process has similarities to evolution. The ancestor of dogs, and the ancestor of horses, were not like the animals we know today. If what I've heard is accurate, horses were small animals, bred larger for war.

Series of theoretically genetically distinct species in the geologic column - hence, a conduit down which life was passed, right back to the first in the series.

life does not form a series. It forms a tree, which is expected of evolution. note that you haven't actually advanced a theory for how this occurs: you've just said that some intelligent chap got it all going. have you actually tried working out the details? How is the code passed on, and activated in future generations? How does it avoid being destroyed by mutation, which we know occurs? If you take a guess, you have a hypothesis, which you can try to test. That will make you the most advanced ID researcher in the world. I'm really not kidding.

Information technology devices in every cell, theoretically capable of scanning in environmentally relevant information and of working in concert with (presumably quantum category) signals permeating the biosphere, to trigger species transformation and re-programming.

you can say that a fairy did this all you like, but the evidence is still saying evolution. have you seen that evidence, and do you understand why?

Discovery that 'toolkits' for 'building' organic structures in future species, were present in other species long before the 'building' was triggered. (E.g, HOX genes in paddlefish, seemingly waiting to be activated by some future trigger. See SCIENCEDAILY on this topic.)

but these genes still behave in a way expected of evolution. for example, suppose that you're an animal a billion years in the past, and you've evolved a nice functional body which happens to be ancestral to all life on Earth today. All the other animals after you will inherit your body plan, and if it happens to be a pretty successful one, it won't change a lot. Stasis is just as much a part of evolution as change, and if you study it you'll find out where it applies and where it doesn't.

Perhaps some basic analytical investigation is appropriate?

What creationists don't tell you is that this investigation has been, and is being done. Their spin of this into 'evolutionists are ignoring arguments' is very dishonest. You seem a little more honest, so perhaps you won't repeat these errors?

David Stanton · 13 April 2008

Am I the only one who sees that Behe's Backer has a writing style that is creepy in it's similarity to the troll Philip? He was asked repeatedly to explain himself and answer questions and he refused. Now it appears he is back and thinks that he can fool everyone into thinking that his arguments are valid because he has chosen a different name.

Consider the metaphysical nonsense, the sentence fragments, the disjointed facts spewed out appropo of nothing, the question marks at the ends of noniterogative statements, the random use of capital letters, the almost incomprehensible mangling of idioms, the insistence on quantum computers of an organic nature, etc., etc. etc. One could go on at length, but why would one?

Please, if this guy is stupid enough to be using the same computer to make the same arguments, ban him according to the rules. The children will thnk you for it in the morning. If no evidence exists to support my contention, then never mind. Everyone should feel free to respond to his nonsense until he is banned, but I don't intend to dignify him with any more responses.

At least you can send him to TBW. His post is so wildly off-topic it would certainly be appropriate.

David Stanton · 13 April 2008

Man, I stopped reading that stuff half way through. HOX genes and SCIENCEDAILY, Now I know it's Phil.

Venus Mousetrap · 13 April 2008

forget my last sentence :)

Ian Musgrave · 13 April 2008

That is odd. I evolve protein- protein binding sites all the time. So does everyone else and the cats or they are dead. This is the whole basis of adaptive immune systems, B and T cells. Gee, unknown intelligent agents floating around in my blood stream. Who knew and when?
— Raven

Behe claims the immune system is "different", it's designed to throw up lots of binding sites

The elegant immune system is deigned to saturate shape space. But the situation is entirely different inside the cells, For cellular proteins there is no built in mechanism to deliberately make new binding sites ... In general the only way to get a new sequence from for a cellular protein is over many generations by random mutation. Searching through shape space with cellular proteins is glacially slow and abysmally inefficient.
— Behe

Behe does briefly acknowledge that the immune system works via random mutation and selection, but then breezes on with a "Look, it's all so fast". It's the selection step that he ignores. The immune system is much quicker, as the immunoglobulin genes are rapidly mutated. But it is made much more efficient by having a panel of weakly binding receptors, of which the best are selectively mutated, then the next best selected and so on. The selection aspect is buried away and de-emphasized, just as the selection aspect is ignored for generation of standard binding sites. As I said, for someone who claims to accept natural selection, Behe sure ignores it a lot.

Mike Elzinga · 13 April 2008

Am I the only one who sees that Behe’s Backer has a writing style that is creepy in it’s similarity to the troll Philip?

David, Wow! I just returned to find this. I agree; it is creepy. After looking around on PBH’s site, I would say the writing style is almost identical with the exception of a few synonyms as replacements for terms he has used here and on his site (e.g., “entropy barrier” = “entropy hurdle”)

Before we start, a note on the quite professional and totally relevant presentation at the head of this page: it tells us that changes can, at least theoretically, occur in the incredibly sophisticated information carriers/controls within cells. What it conveniently neglects to mention, are the remarkable recent advances in nanotechnology, quantum physics, quantum computation, etc., especially the hints that are coming through, of the possibilities in relation to complex organic molecules. It turns out that dull old carbon, is anything but dull, when you get down to the atomic level. Every technical fact presented above, testifies in some way to information technology; and the information technology - a natural phenomenon - points the way to overcoming the entropy hurdle and to an explanation of the unfolding of life within the parameters set by physical chemistry.

This is the central theme of PBH’s pseudo-science. In fact, it is essentially the outline I posted using excerpts from his site. And this is the ethics of someone who claims to see God. Why am I not surprised? I agree that the Bathroom Wall is the appropriate place for his comments.

SWT · 13 April 2008

Behe's Backer : Your disagreement isn't with Behe, it's with Galileo, Newton, Einstein - possibly with Darwin, himself, and certainly with mathematics, physics, and reason.

I'm quite certian that my disagreement is with Behe. Galileo, Newton, Darwin, and Einstein proposed testable hypotheses that were compatible with the previously available data. Those following made additional observations that resulted in improvements to the original theories.

We have had the junk yard converting to a cadillac by blind chance, so repeatedly, I won't belabour anyone by pursuing it.

You guys really need some new material. One of the mechanisms included in MET is random variation + natural selection. The selection is not blind chance, and as one poster argued persuasively many threads ago, natural selection actually meets Dembski's criterion of intelligence (the ability to select among alternatives).

But since we here claim the technical truth for evolution, and since there was a sequential unrolling of species, let's stand a few facts up and test theories. Before we start, a note on the quite professional and totally relevant presentation at the head of this page: it tells us that changes can, at least theoretically, occur in the incredibly sophisticated information carriers/controls within cells.

Actually, the presentation tells us that changes occur in fact within the genome of a cell.

What it conveniently neglects to mention, are the remarkable recent advances in nanotechnology, quantum physics, quantum computation, etc., especially the hints that are coming through, of the possibilities in relation to complex organic molecules. It turns out that dull old carbon, is anything but dull, when you get down to the atomic level. Every technical fact presented above, testifies in some way to information technology; and the information technology - a natural phenomenon - points the way to overcoming the entropy hurdle and to an explanation of the unfolding of life within the parameters set by physical chemistry.

Organic chemists have known for quite a while that the chemistry of "dull old carbon" can be facinating. The technical facts above point to some very interesting chemistry that is occurring within an extremely complex set of autocatalytic reactions. What is the "entropy hurdle" to which you refer? Living cells have a continual influx of energy that allows them to maintain non-equilibrium structures.

Series of theoretically genetically distinct species in the geologic column - hence, a conduit down which life was passed, right back to the first in the series.

No, series of almost certainly genetically distinct species in the geologic column if you take "genetic snapshots" at long enough intervals. I suppose you can view it as a "counduit down which life was passed, right back to the first of the series" -- just remember that MET also posits that modern organisms on this planet are part of a continuous "tree of life" that reaches back to some original set of living organisms.

Information technology devices in every cell, theoretically capable of scanning in environmentally relevant information and of working in concert with (presumably quantum category) signals permeating the biosphere, to trigger species transformation and re-programming.

Are you suggesting that organisms have mechanisms for modifying their genomes in response to their environment? I'm not aware of any work demonstrating this. Then again, I'm not a biologist, so feel free to point me to some peer-reviewed research that verifies this. I have pretty good journal access, so feel free to go to the real, hard-core technical literature on this.

Discovery that 'toolkits' for 'building' organic structures in future species, were present in other species long before the 'building' was triggered. (E.g, HOX genes in paddlefish, seemingly waiting to be activated by some future trigger. See SCIENCEDAILY on this topic.)

Homologous genes are pretty much old news, aren't they?

Perhaps some basic analytical investigation is appropriate?

That's what many biologists are actively doing. If the ID proponents really have what they think is a working theory, they should do the same -- get themselves into a lab and do some research.

Richard Simons · 13 April 2008

Am I the only one who sees that Behe’s Backer has a writing style that is creepy in it’s similarity to the troll Philip?

It was the "unfolding/unrolling of living forms" that struck me as pure PBH. PBH - I am still waiting for an apology.

Mike Elzinga · 13 April 2008

Just for the record, here is some documentation.

Before we start, a note on the quite professional and totally relevant presentation at the head of this page: it tells us that changes can, at least theoretically, occur in the incredibly sophisticated information carriers/controls within cells. What it conveniently neglects to mention, are the remarkable recent advances in nanotechnology, quantum physics, quantum computation, etc., especially the hints that are coming through, of the possibilities in relation to complex organic molecules. It turns out that dull old carbon, is anything but dull, when you get down to the atomic level. Every technical fact presented above, testifies in some way to information technology; and the information technology - a natural phenomenon - points the way to overcoming the entropy hurdle and to an explanation of the unfolding of life within the parameters set by physical chemistry.

This is the central theme of PBH’s pseudo-science, namely, that “superconduction” plus gravitation and the Sun-Earth-Moon system as providing the “information” that is transmitted to DNA. In fact, it is the outline I posted here and further expanding on it here using excerpts from his site. Here are PBH’s “quantum computation” site and his “planetary magnetism” site .

David Stanton · 13 April 2008

SWT,

Good luck. Mike has been asking him to explain the "entropy barrier" for a week and for some reason he just doesn't want anyone else to understand it. That seems to be why he changed his handle, so he could avoid questions.

I guess he thinks that entropy somehow requires information in order to be overcome, rather than just energy. Hence the need for a quantum computer and photons that are processed by the magnetic field (however that is supposed to work). Anyway, since he refuses to explain what he means I guess we'll never know. Good bet that it is complete nonsense though.

Funny how he thinks that this stuff is necessaray to mention on every thread (no matter what the topic) but not important enough to explain. Oh, he doesn't know anything about hox genes either, so don't bother asking about that.

Dale Husband · 13 April 2008

Since proteins, along with DNA, RNA, and carbohydrates are polymers (molecules made of repeating units) they could be of infinite length and could be combined in an unlimited number of ways. That alone discredits the concepts of "irreducible complexity" and "complex specified information" that Intelligent Design promoters like Michael Behe and William Demski made issues of many years ago. NOTHING can be irreducibly complex if its parts can be broken down and assembled differently! And specified complexity is such a subjective thing that it is scientifically meaningless.

fnxtr · 14 April 2008

Like I said: Phil's Timecube Lite.

Romartus · 14 April 2008

In fact, it is the outline I posted here and further expanding on it here using excerpts from his site.

Here are PBH’s “quantum computation” site and his “planetary magnetism” site .

I checked the links. I have noticed creationists have a method of writing in a very convoluted way which involves throwing a lot of "data" at you and then refer you to the Bible. It is like expecting that after reading Hamlet that somewhere buried in there is Shakespeare's thoughts about Dark Matter or something such like. Perhaps it is a writing style that is an attempt to bamboozle credulous people into thinking these guys might be on to something....

Mike Elzinga · 14 April 2008

Romartus: In fact, it is the outline I posted here and further expanding on it here using excerpts from his site. Here are PBH’s “quantum computation” site and his “planetary magnetism” site . I checked the links. I have noticed creationists have a method of writing in a very convoluted way which involves throwing a lot of 'data' at you and then refer you to the Bible. It is like expecting that after reading Hamlet that somewhere buried in there is Shakespeare's thoughts about Dark Matter or something such like. Perhaps it is a writing style that is an attempt to bamboozle credulous people into thinking these guys might be on to something....

Fixed Romartus' post.

Rick R · 14 April 2008

Like I said about PBH on another thread: a moron with a thesaurus is still a moron.

Ichthyic · 14 April 2008

Perhaps it is a writing style that is an attempt to bamboozle credulous people into thinking these guys might be on to something….

or maybe -just maybe-

they're in serious need of some mental health care.

Torbjörn Larsson, OM · 14 April 2008

Compliments for a very stimulating essay, which covered much undiscovered ground for this layman. On PBH as BB: in all likelihood. I also notice such ideas that modern science is fundamentally wrong, and that AIG is supported by describing evolution as biology has found it to be. @ PBH: Why can't you describe what you think an "entropy barrier/hurdle" is? Eager minds wants to know!

We have had the junk yard converting to a cadillac by blind chance, so repeatedly, I won’t belabour anyone by pursuing it. But since we here claim the technical truth for evolution, and since there was a sequential unrolling of species, let’s stand a few facts up and test theories.

Misrepresenting evolutionary biology as it is observed ("blind chance", "unrolling") shows that you would do well to study what you incessantly try to pontificate on.

Which of these two proposals - chance selective breeding on the one hand, and information- driven pathways on the other, is supported by the following?

Note: Selection is AFAIU a contingent process with deterministic outcome, compare with QM propagation of states for example. "Chance" is then not a correct descriptor. The main point is that the natural based theory is even for a layman obviously simpler and consistent with current observations; no frontloading mechanism necessary nor observed. Which btw currently invalidates all frontloading ideas as predictive frontloading 'theories'; no mechanism has been proposed. The information could as well be "poofed" into existence at any time. Sound familiar? At the same time the scientific theory is wider and validated by more observations than 'frontloading' pseudoscience tries to tackle; it explains vestigial organs for example. So from a scientific standpoint there can be no contest.

Perhaps some basic analytical investigation is appropriate?

So 150+ years of intense empirical theory-based investigation isn't enough for you? What do you then mean with "some"? Can you explain that in some detail, or is that another "entropic hurdle" for you?

Torbjörn Larsson, OM · 14 April 2008

they’re in serious need of some mental health care.

That observation leads to hard moral judgment call IMHO. Obviously, as in such famous cases as of Larry Fafarman, there can be independent evidence for severe mental health problems. In other cases such as recently trolling keith, the unhinged irrationality and emotional attitude points to it. In such cases the appropriate attitude can be to fully abstain supporting a behavior that strengthens the underlying problem. In other cases it can be as much a badly expressed dependence problem. Still a health problem if serious, but there is degrees where the moral act of supporting science in the face of antiscience can overtake the moral act of denying support for a dependence. I'm acting on the later in such cases. Sure, added characteristics for example antiscience woo sites and narrowly repetitive behavior can indicate other mental problems. But it can as easily be a severe case of incompetence (remember, incompetents are verifiable incompetent to observe their own insufficiency) coupled to the type of rigid personality incompetence supports. It is impossible to 'diagnose' for a layman and over the web.

paragwinn · 14 April 2008

A very enlightening post. Thank you and keep up the good work.

Nigel D · 14 April 2008

Ian, thanks for another very readable and informative post.

I deduce from Behe's ramblings that it is far too long since he tried to express and purify a protein in the lab. If he had done, he would know that protein-protein binding sites are cropping up all the time, and often present a barrier to purifying a mammalian protein from a bacterial expression system.

Sometimes, when expressing a mammalian gene in a bacterial system, a bacterial protein will purely by chance exhibit tight binding to the protein of interest. After all, since most of the surface residues on a soluble protein will be capable of participating in hydrogen bonding, it is not surprising that, from the thousand or so proteins expressed by E. coli, one occasionally sees one that possesses a pattern of residues that is complementary to a part of the surface of one's protein of interest.

Ian Musgrave · 14 April 2008

All the Phil Heyward stuff and comments has been moved to the Bathroom Wall, you can continue that conversation over there. (Please, don't feed the trolls here).

David Stanton · 14 April 2008

Thanks Ian.

David vun Kannon, FCD · 14 April 2008

Thank you for including the visuals in a very informative post. They really helped drive home the points.

The point that it is the shape, charge, etc. of the surfaces, rather than the linear codon sequences, that matter undercuts the argument from improbability very well. Is there a canonical version of this counter-argument?

Mike Elzinga · 14 April 2008

Ian Musgrave: All the Phil Heyward stuff and comments has been moved to the Bathroom Wall, you can continue that conversation over there. (Please, don't feed the trolls here).

Thank you, Ian. And thanks for the great thread. I really enjoy seeing these kinds of details being filled in.

Ian Musgrave · 14 April 2008

I deduce from Behe’s ramblings that it is far too long since he tried to express and purify a protein in the lab. If he had done, he would know that protein-protein binding sites are cropping up all the time, and often present a barrier to purifying a mammalian protein from a bacterial expression system.
— Nigel D

I don't think he's ever done anything like that. He's a DNA structure man, and was a key player in understanding the B-Z transition in DNA. Proteins he hasn't played with. Heck, if he had done any radioligand binding, antibody pull down (sob) etc., he would know all about protein-protein interactions cropping up everywhere. But I'm sure Behe will have some way to dismiss these observations.

Ian Musgrave · 14 April 2008

Is there a canonical version of this counter-argument?
— David vun Kannon, FCD

Not as such. All this stuff is in the scientific literature, but it's never been assembled before for the purpose of confronting Behe's misrepresentations.

raven · 14 April 2008

Actually protein protein binding is so common and reasonably well understood that no biologists think it is at all unusual or magical. Mark Ptashne designed a portable transcription activating domain 20 years ago. The requirements are pretty relaxed, a short amphipathic alpha helix, a common protein motif. With low sequence specificity requirements, mutational creation and modulation by RM + NS would be considered easy. Behe's books reduce down to Arguments from Ignorance and Incredulity. "I can't see how my foot evolved so god exists." or "I don't know anything and have no intention of removing my blindfold."

1: Nature. 1987 Dec 17-23;330(6149):670-2. Transcription in yeast activated by a putative amphipathic alpha helix linked to a DNA binding unit.Giniger E, Ptashne M. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138. Gene activation by a DNA-binding regulatory protein in yeast requires the protein to have two components: one to recognize a specific DNA sequence and a second, the 'activating region', to interact with a general transcription factor or perhaps with RNA polymerase. The activating regions that have been characterized are acidic, and mutational analysis of one indicates that this acidity is important for activity. Here we report the design of an artificial protein bearing a novel 15-amino acid peptide linked to a DNA binding fragment of the yeast regulatory protein GAL4). The synthetic peptide is acidic and should it form an alpha-helix, that helix would be amphipathic, having one hydrophilic face bearing the acidic residues, and one hydrophobic face. When expressed in yeast, the artificial protein bearing this peptide efficiently activates the GAL1 gene which is ordinarily activated by GAL4. An otherwise identical protein with the novel 15 amino acids in a scrambled order, and which is thus unable to form an amphipathic structure, does not activate GAL1 transcription.

Nigel D · 15 April 2008

I don’t think he’s ever done anything like that. He’s a DNA structure man, and was a key player in understanding the B-Z transition in DNA.
— Ian Musgrave

Ah, that would explain why I had not heard of him before I started reading TalkOrigins and Panda's Thumb. I have never done much work with DNA in the lab. Most of my work has been with proteins (I work in the biopharmaceuticals industry).

Proteins he hasn’t played with. Heck, if he had done any radioligand binding, antibody pull down (sob) etc., he would know all about protein-protein interactions cropping up everywhere.

I have been fortunate enough to not need to perform those analyses, but I am sure that, like so many other techniques, these assays are never as easy as the literature would have us believe. (But then, if it was easy, anybody could do it!)

But I’m sure Behe will have some way to dismiss these observations.

I'm sure he will think he can. My own feeling is that these incidental interactions (some of which are surely non-specific, but some of which are simply too strong for non-specific binding to be a convincing explanation) indicate that Behe has got the whole thing backwards. The challenge for the cell is not to develop new and useful protein-protein interactions. The challenge is to prevent protein-protein interactions, except where they are beneficial.

ievolved · 15 April 2008

I think Behe has got a point.

ievolved · 15 April 2008

You mix alot of them green and red stringy things in a soup of stuff, add a bit of heat. Wait a zillion years and before you know it you have consciousness. Simple really.

Henry J · 15 April 2008

ie,
The first step in constructing an argument is to learn what the other side is saying. Think about it.

bigbang · 13 May 2008

Ian Musgrave says: “Behe claims that for even a simple binding site composed of two amino acids in specific locations that you would need a population of around 1020 organisms to evolve it.”

Well, not quite. As. Musgrave probably knows, Behe discusses in his EoE how a single mutation has indeed resulted in a change in the hemoglobin protein site causing sickle cell in humans which provides protection against malaria, but which is actually a degradation of hemoglobin making it less efficient and, unfortunately, also causing sickle cell disease in those individuals having two sickle cell genes, one from each parent.

Also, as many here don’t seem to appreciate, the 10^20 figure is not a probability calculation determined by Behe. Rather it’s a determination made from actual data. (Got that? Actual data.) It’s a determination made by Malaria expert N J White----he determined that it took a population of around 10^20 organisms b/f the Malaria parasite, via random mutation and selection, finally developed resistance to CQ, which required two mutations (apparently not by “simple step by step selectable paths)”.

Finally, as I believe Behe has already explained to Musgrave in one of their back-n-forths, and as noted in Chapter 8 of EoE, the HIV virus has undergone enough mutating in past decades to form all possible viral-viral binding sites, and as Behe originally (and mistakenly) commented in the book, that apparently none of them had been helpful . . . although he now realizes that one of them apparently did help after-all (apparently resulting in one new binding site) via random mutation and selection; but that, similar to the two mutations in the malaria parasite providing CQ resistance, random mutation and selection had to go through around 10^20 viruses to achieve that result.

(Again, this 10^20 figure is not Behe’s estimate or determination of the probability of two “simultaneous” mutations; rather it’s what actual data in he real world tells us that was actually required to get the two mutations that provided malaria with CQ resistance, and what was actually required for HIV to acquire the mutations to evolve the above mentioned viral protein-viral protein binding site; regardless of what anyone here happens to believe about simple step by step selectable paths to protein-protein binding.)

So based on actual available data, rather than just so stories, we conservatively estimate that random mutation and selection required around 10^20 organism to evolve one good protein binding site (which apparently requires at least two mutations----that apparently aren’t attained via “simple step-by-step selectable paths”----and also that is not ultimately a degradation), which means that two new sites would require 10^40 organisms (10^20 *10^20); and considering that it’s been estimated (by others, not by Behe) that there’ve been less than 10^40 cells in Earth’s 4 billion year history, and that most proteins in the cell operate as specific complexes of six or more chains, it looks like Behe’s two-binding-site rule is a reasonable estimate of the edge of evolution via random mutation and selection.

And BTW, as Behe has always maintained, the evidence for common descent is fairly convincing, so common descent isn’t and never has been an issue.

Although life certainly has and continues to evolve, or unfold as it were, the core issue is how much evolution can actually and reasonably be explained as being a result of random mutation and selection. It’s becoming more and more obvious that neo-Darwinian evolution by random mutation and selection is an incomplete theory at best, explaining little more than the microevolution that we can often observe.

Robb Massey · 19 June 2008

I believe Behe actually addresses this sort of phenomena in the footnotes in chapter 8. On page 152, he states: "With a couple of interesting exceptions,(6) protein-protein binding isn't the result of processes analogous to breaking a vase or water freezing around a complex shape. It arises either from searching a huge shape-space library, as the immune system does, or by some nonrandom mechanism".

Footnote 6 (page 293) states the following:
"Proteins sometimes take on the altered shapes of other proteins in neurological diseases such as Alzheimer's (Dobson, C.,M.2002. Protein-misfolding diseases: getting out of shape. Nature 418:729-30). Also, some proteins that bind copies of themselves are thought to have arisen by "domain swapping." That is, areas called "domains" that had been in contact in a single protein instead bind to the analogous region of a second copy of the protein. This scenario does not propose that new binding sites arose, just that pre-existing binding sites got mixed up (Rousseau, F., Schymkowitz,J.W., and Itzhaki, L.,S. 2003. The unfolding story of three-dimensional domain swapping. Structure 11:243-51).

Doesn't the ribonuclease example fall into the "domain swapping" category? Is what we see in this example sufficient enough to assemble new molecular machinery without relying on ANY of the types of protein binding that we see in sickle cell and HIV (VP1)? I could be missing something here but I don't find this to be all that threatening to Behe's thesis. I'm also not a biochemist (just interested in the topic) and I don't have much of a "biochemical imagination", but at face value I can't even begin to imagine how 'domain swapping' could be responsible for the raw material of nearly everything we see in biology (which, if Behe's claims that new protein-protein sites are correct, is necessarily true unless there is some other way). To me this would seem similar to trying to hand paint a colored picture when you only have black and white to mix with.

Regardless though, I think it's wrong to say that Behe does not address this in the book. Even if you disagree with the way he addresses it, he didn't ignore it altogether.

Ian Musgrave · 20 June 2008

Robb Massey said: I believe Behe actually addresses this sort of phenomena in the footnotes in chapter 8. On page 152, he states: "With a couple of interesting exceptions,(6) protein-protein binding isn't the result of processes analogous to breaking a vase or water freezing around a complex shape. It arises either from searching a huge shape-space library, as the immune system does, or by some nonrandom mechanism".

Statements that have nothing to do with the issues at hand can hardly be said to be "addressing the issue".

Footnote 6 (page 293) states the following: "Proteins sometimes take on the altered shapes of other proteins in neurological diseases such as Alzheimer's (Dobson, C.,M.2002. Protein-misfolding diseases: getting out of shape. Nature 418:729-30). Also, some proteins that bind copies of themselves are thought to have arisen by "domain swapping." That is, areas called "domains" that had been in contact in a single protein instead bind to the analogous region of a second copy of the protein. This scenario does not propose that new binding sites arose, just that pre-existing binding sites got mixed up (Rousseau, F., Schymkowitz,J.W., and Itzhaki, L.,S. 2003. The unfolding story of three-dimensional domain swapping. Structure 11:243-51).

A couple of lines dismissal is also not "addressing the issue". Given that the vast majority of the 10,000 or so protein-protein interactions have arisen by just the methods that he dismisses airily, this is something he should have addressed up front and in detail (hint how did the huge protein kinase family interactome arise). Furthermore, he says some proteins have domain structure, when in fact the vast *majority* of proteins have multi-domain structure, and domain swapping or acquisition is a major source of new function and/or binding. For example acquiring PX domains is a major reason for retargetting proteins, and acquiring SH domains allows protein to assemble into multi-protein complexes. To handwave away a major source of the 10,000 protein-protein interactions he goes on about is not "addressing the issue". He also limits "domain swapping" to proteins binding themselves, but it also applies to proteins binding non-identical proteins (again, PX or SH domains being swapped between different proteins etc.), and is again a major source of new binding interactions.

Doesn't the ribonuclease example fall into the "domain swapping" category?

Yes, once more, a couple of lines dismissal (and misrepresenting the issue as well) is also not "addressing the issue".

Is what we see in this example sufficient enough to assemble new molecular machinery without relying on ANY of the types of protein binding that we see in sickle cell and HIV (VP1)? I could be missing something here but I don't find this to be all that threatening to Behe's thesis. I'm also not a biochemist (just interested in the topic) and I don't have much of a "biochemical imagination", but at face value I can't even begin to imagine how 'domain swapping' could be responsible for the raw material of nearly everything we see in biology (which, if Behe's claims that new protein-protein sites are correct, is necessarily true unless there is some other way). To me this would seem similar to trying to hand paint a colored picture when you only have black and white to mix with. Regardless though, I think it's wrong to say that Behe does not address this in the book. Even if you disagree with the way he addresses it, he didn't ignore it altogether.

Again, a couple of lines of dismissals (which misrepresent the issue anyway) are not "addressing the issue". Also, failure of imagination is not an argument either. I've given examples of the large number of protein families that your body is using right now that are either homomultimers (as well there is also things like Gro-el, a range of replication and repair factors), or heteromultimers that have originated by divergence of homomultimers (again, there are many more than just my list, a recent paper examined around 8,000 of these proteins, a sizeable fraction of the vertebrate proteome). From ion channels to elongation factors to the cellular rubbish bin, these diverse and crtical bit of cellular machinery were all built by the mechanisms that dimerise ribonuclease. Remember, most of what we see in biology is a slightly modified version of something else, the huge apparent diversity of protein structures and binding is mostly variation of just a few themes.

Robb Massey · 9 July 2008

Dr. Musgrave, Thanks for taking the time to reply. I have to admit that when it comes to understanding biochemical processes and terms, I am to a biochemist what a gringo who speaks broken Spanish is to a Mexican...so there is a good chance that what I am about to ask is out of ignorance. I generally understand these things best when comparing them to other processes I am familiar with such as factories, mousetraps, software engineering, etc even though it may not always translate perfectly. That is one reason I love the way Michael Behe writes; it is still easy for knuckleheads like me to follow! That being said, I humbly ask that for my own sake your responses are simple (if you choose to respond, and I hope you do).

Ian Musgrave said: A couple of lines dismissal is also not “addressing the issue”. Given that the vast majority of the 10,000 or so protein-protein interactions have arisen by just the methods that he dismisses airily, this is something he should have addressed up front and in detail (hint how did the huge protein kinase family interactome arise). Furthermore, he says some proteins have domain structure, when in fact the vast *majority* of proteins have multi-domain structure, and domain swapping or acquisition is a major source of new function and/or binding. For example acquiring PX domains is a major reason for retargetting proteins, and acquiring SH domains allows protein to assemble into multi-protein complexes. To handwave away a major source of the 10,000 protein-protein interactions he goes on about is not “addressing the issue”. He also limits “domain swapping” to proteins binding themselves, but it also applies to proteins binding non-identical proteins (again, PX or SH domains being swapped between different proteins etc.), and is again a major source of new binding interactions

I have a few questions related to this: 1. If I understand you correctly, if this type of variation were to occur in a network formerly of 10 interacting protein-protein binding sites, then the network could now consist of 11 protein-protein binding sites? 2. Is it an established fact that the 'vast majority' of the 10,000 protein-protein binding sites arose this way (were they observed), or is it just a likelihood? 3. What sort of rate do you think could be attributed to these types of bindings, as observed in ribonuclease (and evidently other structures such as ‘protein kinase family)? How often would you say we observe them in experiments? Is ribonuclease a rare observation or are there other observations? Did we observe the protein kinase family interactome's evolution that you refer to or does it just appear to have arisen this way? please note I'm not referring to systems that appear to have arisen this way; I'm referring rather to how often we observe new instances via observation) 4. What is the "vast majority" you are referring to? Is it 8,500 binding sites out of the 10,000? 9,500? 9,998? If we assume that we can scrap a huge number of the 10,000, doesn't that still leave a raw amount that must answer to the edge? If for instance, the "vast majority" was 9,000, would you be content if Behe lowered the chart's maximum # of relevant protein-protein binding sites from 10,000 to 1,000? If the e. coli, sickle cell, and HIV experiments cited in EOE are of any indication, it still seems like an incredible mountain to climb. To me that's sort of like reducing the number of miles one has to swim from 10 bajillion to just a bajillion.

Also, failure of imagination is not an argument either. I’ve given examples of the large number of protein families that your body is using right now that are either homomultimers (as well there is also things like Gro-el, a range of replication and repair factors), or heteromultimers that have originated by divergence of homomultimers (again, there are many more than just my list, a recent paper examined around 8,000 of these proteins, a sizeable fraction of the vertebrate proteome). From ion channels to elongation factors to the cellular rubbish bin, these diverse and crtical bit of cellular machinery were all built by the mechanisms that dimerise ribonuclease.

I already asked this question but it’s a crucial one so I will repeat it in respect to this paragraph: the ‘mechanisms’ that dimerise ribonuclease…how often do we see those mechanisms at play in laboratory experiments? Are the examples that you cited observed or implied? **Also, the paper you mention examining 8,000 proteins may be the answer to question #4 but I'm unclear if the paper refers to just the ones found in the 10K human cell) Sincerely, Robb