Scientific errors in Christadelphian attacks on evolution: The Testimony magazine - 2

In 1996, biochemist Michael Behe published "Darwin's Black Box": The Biochemical Challenge  to Evolution" [1] which was universally panned by scientifically informed critics who recognised its numerous errors. Four years later, David Burges, science editor of the Testimony, published a superficlal, uncritical review of the book. [2] Not only did his review show that he knew little about evolutionary biology, he inadvertently misled his readers by failing to point out that mainstream scientists four years earlier had refuted Behe's book.

Behe's argument is that there exist structures at the cellular level that are so complicated that if a single component was missing, the structure would fail to work. Furthermore, he argues that this precludes them arising via a gradual, Darwinian approach. Burges never critically engages with Behe's book. but rather regurgitates its claims unchallenged:

It is clear just how critical the various parts of this cascade are. If any were missing, the next protein in the sequence would not be formed and clotting would fail to occur. If the controlling stages were not present, clotting would continue until the whole circulatory system went solid. In order to work, the whole system of proteins must be precisely balanced and complete. Indeed, we know well that diseases such as haemophilia and stroke are the direct result of deficiencies in the blood coagulation system. Yet evolution must explain how such a mechanism came into existence in small steps and was still fully effective in protecting the lives of the animals in the supposed evolutionary sequence.

Other examples described by Behe with admirable clarity include: 

• the biochemical basis of vision; the eye has always presented a major problem to Darwinists, but the complexity of the biochemistry of vision compounds it; 

• the structure of cilia, minute beating hairlike structures that enable single-celled creatures to swim and feed, and remove foreign bodies from our respiratory system; 

• the cell transport system, which moves waste products within the cell to a structure called the lysosome, for removal from the cell; 

• the immune system, which enables the body to identify and destroy a vast range of foreign organisms.

 All of these are shown to be irreducibly complex systems requiring the presence of many biochemical components, each of which is essential to the correct functioning of those systems. Although these systems have been thoroughly described, very few attempts have been made to show how they could have evolved, and Behe’s case is that they must have been designed as complete functioning systems. His thesis is, of course, a modern extension of the classical argument, first systematically elaborated by William Paley at the end of the eighteenth century, that design in nature demands the existence of an intelligent Designer. 

Ignoring the fact that Burges has merely invoked the tired speciall creationist argument from personal incredulity ('I can't imagine how it evolved, therefore it never evolved') he has failed to tell his readers that not only has Behe's concept of 'irreducible complexity' been shown by biologists to be in error, he has also failed to show that Behe's claims about the alleged irreducible complexity of structures such as the blood clotting cascade have been shown to be false. I will show what Burges has neglected to tell his readers about irreducible complexity.

1. Behe's thesis has been overwhelmingly rejected by mainstream scientists

Burges' article was published in 2000, three to four years after Behe's thesis was shredded  by everyone outside the special creationist community. Cell biologost Kenneth Miller - a devout Catholic active in showing that science and religion are not in conflict - observed that:

If Behe's formulation of intelligent design as science is illogical, his mechanism for how the work of the designer was inserted into living systems is almost laughable. Remember that Behe accepts the validity of the geological ages and the fossil record - an open-minded scientist can hardly do otherwise - and yet he claims that the complex biochemical systems he extols were fashioned by an intelligent agent. When did this agent go to work, and when were the genes encoding them engineered? He has an answer ready:

"Suppose that nearly four billion years ago the designer made the first cell, already containing all of the irreducibly complex biochemical systems discussed here and many others. (One can postulate that the designs for systems that were to be used later, such as blood clotting, were present but not "turned on." In present-day organisms plenty of genes are turned off for a while, sometimes for generations, to be turned on at a later time.)"

This means that billions of years ago a humble prokaryote was packed with genes that would be turned off for hundreds of millions of years before they produced the eukaryotic cilium, and genes for blood clotting proteins that would pass more than a billion inactive years in genetic "cold storage." And what happens during those billions of years? As any student of genetics will tell you, because those genes are not expressed, natural selection cannot weed out genetic mistakes. This means that mutations will accumulate in these genes at breathtaking rates, rendering then hopelessly changed and inoperative hundreds of millions of years before Behe says that they will be needed. [3] 

His concept of ‘front-loading’ as Miller points out is unsustainable. If a gene is selectively neutral, then it will accumulate mutations that will eventually cripple it. Genes for ‘irreducibly complex systems’ that were not active would be riddled with genetic mistakes and crippled well before they were needed.

Robert Dorit was equally critical, noting that Behe was willing to accept that Darwin's argument applied at the macroscopic level of life, but not at the molecular level. Behe's argument therefore relied on a boundary between the microscopic and macroscopic world which does not exist:

By the author's own admission, the Darwinian argument appears to suffice in accounting for design at visible levels of organization—bird flight or the hydrodynamic design of aquatic organisms. Only at the molecular level does the argument somehow fail. But, in fact, there is no fundamental discontinuity between the molecular and the supramolecular level in biology. The traditions, tools and approaches of the molecular biologist may differ radically from those of the functional morphologist, but the fabric of living systems is seamless. There is nothing that makes design at the molecular level any more special than design or organization at any other level in biology. If anything, molecular design may be somewhat easier to account for, because the components of molecular machines are frequently the products of identifiable genes. [4]

Jerry Coyne's penetrating review exposes another flaw in Behe's thesis; the allegedly irreducibly complex molecular pathways:

"...did not evolve by the sequential addition of steps to pathways that became functional only at the end. Instead, they have been rigged up with pieces co-opted from other pathways, duplicated genes and early multifunctional enzymes. Thrombin, for example, is one of the key proteins in blood-clotting, but also acts in cell division, and is related to the digestive enzyme trypsin. Who knows which function came first? Behe makes a few half-hearted attempts to build up such pathways, but quickly abandons the enterprise and cries 'design.' 

"...we have plenty of direct evidence for the evolution of molecules. This includes the remarkable congruence between phylogenies based on anatomy and those based on DNA or protein sequence (bat haemoglobin, for example is far more similar to that of whales than of birds), the relatedness of genes through gene duplication (including those involved in the immune system and blood-clotting), and the existence of vestigial 'pseudogenes' that were useful in ancestors. (Unlike most mammals, humans cannot synthesize vitamin C; we still carry the gene for the final step in this pathway, but deletions have rendered it non-functional.)" [5]

Perhaps the most devastating critique of Behe's thesis came from the evolutionary biologist H Allen Orr:

Behe's colossal mistake is that, in rejecting these possibilities, he concludes that no Darwinian solution remains. But one does. It is this: An irreducibly complex system can be built gradually by adding parts that, while initially just advantageous, become—because of later changes—essential. The logic is very simple. Some part (A) initially does some job (and not very well, perhaps). Another part (B) later gets added because it helps A. This new part isn't essential, it merely improves things. But later on, A (or something else) may change in such a way that B now becomes indispensable. This process continues as further parts get folded into the system. And at the end of the day, many parts may all be required. 

The point is there's no guarantee that improvements will remain mere improvements. Indeed because later changes build on previous ones, there's every reason to think that earlier refinements might become necessary. The transformation of air bladders into lungs that allowed animals to breathe atmospheric oxygen was initially just advantageous: such beasts could explore open niches—like dry land—that were unavailable to their lung-less peers. But as evolution built on this adaptation (modifying limbs for walking, for instance), we grew thoroughly terrestrial and lungs, consequently, are no longer luxuries—they are essential. The punch line is, I think, obvious: although this process is thoroughly Darwinian, we are often left with a system that is irreducibly complex. I'm afraid there's no room for compromise here: Behe's key claim that all the components of an irreducibly complex system "have to be there from the beginning" is dead wrong. [6]

As Orr notes, this evolutionary explanation is hardly new, and has an impeccable pedigree, being advanced by the Nobel laureate and geneticist Hermann Muller as early as 1918:

Most present-day animals are the result of a long process of evolution, in which at least thousands of mutations must have taken place. Each new mutant in turn must have derived its survival value from the effect which it produced upon the “reaction system” that had been brought into being by the many previously formed factors in cooperation; thus a complicated machine was gradually built up whose effective working was dependent upon the interlocking action of very numerous different elementary parts or factors, and many of the characters and factors which, when new, were originally merely an asset finally became necessary because other necessary characters and factors had subsequently become changed so as to be dependent on the former. It must result, in consequence, that a dropping out of, or even a slight change in any one of these parts is very likely to disturb fatally the whole machinery; for this reason we should expect very many, if not most, mutations to result in lethal factors, and of the rest, the majority should be “semi-lethal” or at least disadvantageous in the struggle for life, and likely to set wrong any delicately balanced system, such as the reproductive system. [7]

Irreducible complexity - far from being a challenge to the modern synthetic theory of evolution is readily explained by it. Behe's argument not only has been poorly received by his peers, but had a robust evolutionary explanation nearly 80 years before it was advanced.

Burges wrote his review of Darwin's Black Box in 2000, three years after the latest of these negative reviews was published.  Burges never once engages meaningfully with these reviews, choosing instead to refer to them in the footnotes, and complain that the evolutionists 'label him as a Creationist.' That's unacceptable. Behe's entire thesis has been torn apart, and Burges should have informed his readers of this fact, rather than mindlessly parrot Behe's thesis and imply that all the 'evolutionists' did was call him a 'creationist.'

2. Allegedly 'irreducibly complex' systems such as blood clotting can be explained evolutionarily.

One of Behe's 'icons of irreducible complexity' is the blood coagulation cascade, and far from posing a problem for evolution, it shows all the hallmarks of a system which can be explained by gradual evolution.

I’ve mentioned how Herman Muller nearly one hundred years ago highlighted how this could occur:

[A] complicated machine was gradually built up whose effective working was dependent upon the interlocking action of very numerous different elementary parts or factors, and many of the characters and factors which, when new, were originally merely an asset finally became necessary because other necessary characters and factors had subsequently become changed so as to be dependent on the former.

The example of a co-dependent relationship between two physically disabled married older adults offers an excellent analogy. Originally, both were not frail or disabled, but as time progressed, they began performing for each other tasks that they were not able to do as effectively due to infirmity. Eventually, both became completely dependent on each other for the tasks that the other could perform, to the degree that they formed an ‘irreducibly complex’ unit that could not function without either of them present. To argue that the current co-dependent relationship could not have developed naturally is to make the same mistake that special creationists make when declaring that the flagellum or blood coagulation were too complex to have evolved by chance.

Burges spends some time in his article on blood clotting as an example of irreducible complexity, so it is appropriate that this misconception is corrected. Some of this may come from Behe’s book, since it is not clear when one reads the book how much of the coagulation cascade forms an ‘irreducibly complex’ system. Ken Miller notes in a refutation of allegations made by the intelligent design lobby group The Discovery Institute:

The claim that Michael Behe meant to include only a handful of components from the cascade in his “irreducibly complex” system would come as a shock to anyone who has actually read DBB. Behe describes the system in great detail, asking us to consider the whole system in all its complexity, including each of its 16 different components. In fact, Behe emphasizes how critical each and every component of the system is, pointing out that the absence of certain factors (VIII and IX) cause potentially fatal human diseases (hemophilia A and B, respectively). But then, just as Luskin points out, on page 87, he suddenly seems to retreat, limiting the system to just four factors (fibrinogen, prothrombin, Stuart factor, and proaccelerin). So any suggestion to the contrary is unfair to Behe and ID, right? 

Not so fast. Just keep reading. He doesn’t actually limit his “irreducible core” at all in the way that Luskin now pretends. Instead, on the very next page [p. 87] he discusses the hopelessness of evolution being able to change even a “slightly simplified system” gradually into a “complex, intact system.” Why? Because adding even a single step to the pathway is beyond the range of evolution. As Behe puts it, “From the beginning, a new step in the cascade would require both a proenzyme and also an activating enzyme to switch on the proenzyme at the correct time and place.” Then he drops the bombshell that Luskin seems not to have noticed (or, at least he wasn’t willing to tell his readers about): 

 “Since each step necessarily requires several parts, not only is the entire blood-clotting system irreducibly complex, but so is each step in the pathway.” [DBB, p. 87]

Got that? The “entire blood-clotting system” is “irreducibly complex,” and “so is each step in the pathway.” Which Michael Behe should we believe? The pre-Dover trial one who described the whole magnificent system as an argument for ID? Or the one who flip-flops to a tiny core of just four proteins? Or the one who flip-flops again a page later, and once again says that the “entire blood-clotting system” and each of its steps are irreducibly complex? [8]

It is hard to put confidence in claims the blood coagulation cascade is irreducibly complex when its chief proponent does not consistently define what portion of it is irreducibly complex. If one wants to test the thesis that the human coagulation cascade is irreducibly complex, then the only way to do it is via science. Jiang and Doolittle note that:

Blood clotting follows the same fundamental pattern in all vertebrates, from the early diverging jawless fishes to mammals). In all cases the principal event is the thrombin-catalyzed conversion of a soluble plasma protein, fibrinogen, into an insoluble polymeric fibrin clot. Thrombin is a serine protease, itself the product of a series of proteolytic events. It is well established that all groups of fish…generate thrombin by pathways involving vitamin K-dependent factors, exhibit factor XIII-dependent fibrin cross-linking, and manifest a fibrinolysis that is inhibited by the same agents as inhibit fibrinolysis in mammals. In contrast, thrombin-generated fibrin clotting has not been reported in nonvertebrate chordates or other invertebrate animals. [9]

The authors state the obvious; a complex pathway could not have evolved ‘in one fell swoop’. One hypothesis advanced to explain its gradual evolution was a series of gene duplications and mutations. Comparison of gene sequences of serine proteases have “led to the suggestion that certain of the clotting factors (particularly those constituting the ‘‘contact system’’ involving factors XI and XII, and prekallikrein) must have made their appearance more recently in evolution than some of the other clotting factors and would likely be absent in lower vertebrates.” [10]

To test their hypothesis, the authors took 26 proteins involved in mammal blood coagulation and attempted to see if they had any counterparts in puffer fish and sea squirts. They found that:

In the end, 21 orthologs of the coagulation factor genes were found in the puffer fish genome, but not one authentic ortholog was identified in the sea squirt genome 

On the other hand, the wherewithal for the evolutionary assembly of all of the coagulation factor genes seems to be present in the sea squirt genome in the form of various and sundry domains that in ancestral lines were duplicated and rearranged into the genes for the present-day vertebrate clotting factors. [11]

This has profound implications for the assertion that the blood coagulation cascade is irreducibly complex. The first point is that the puffer fish has a functional coagulation cascade that is missing some of the features that are allegedly essential for the mechanism to work:

It was expected that some components of the ‘‘contact phase’’ system (factors XI and XII, and prekallikrein) would be missing from lower animals because amino acid sequence comparisons showed that factor XI and prekallikrein are so similar that the gene duplication leading to them must have been very recent. Nonetheless, the complete absence of the contact phase system from the puffer fish genome is noteworthy. Of course it cannot be ruled out that one or all of the absent genes do not reside among the 5% of DNA sequence data that are not yet available from the puffer fish. This absence aside, it is remarkable how stable the rest of the coagulation scheme has been over the course of the last 400 million years. [12]

That the puffer fish is able to function adequately without the contact phase part of the ‘irreducibly complex’ coagulation cascade shows that the entire system is not irreducibly complex.

The second point is that the components of the blood clotting proteins are found in the sea squirt, which allows us to readily postulate a plausible mechanism for the evolution of the blood clotting cascade, contrary to Behe’s assertion:

The order of events can also be inferred by considering the most parsimonious route to assembling the various clusters of peripheral domains. Nine of the proteases under discussion can be accounted for by six domain-swapping events …Indeed, the presence of a multiple-kringle protease in the sea squirt genome provides a reasonable model for a step-by-step parallel evolution of the clotting and lysis systems. It should be noted that a serine protease with only one kringle has been found in the ascidian Herdmania momus. Although numerous scenarios have been offered in the past about how modular exchange was involved in generating these schemes…the new genomic data now provide a realistic set of starting materials. [13]

Even further evidence against Behe’s assertion that the coagulation cascade is irreducibly complex is found in a more recent paper by Doolittle (2008) which examines the coagulation system of the lamprey, a basal chordate. Miller notes:

His 2008 paper [Doolittle et al, 2008] reports on a careful search through the lamprey genome. The lamprey, as luck would have it, has a perfectly functional clotting system, and it lacks not only the three factors missing in jawed fish, but also Factors IX and V. 

Now, Luskin could object that Factor IX wasn’t part of his “core,” but Factor V certainly was. And, as Behe pointed out at length, the absence of factor IX causes potentially-fatal hemophilia in humans, which was part of his argument for the irreducible complexity of the whole system. The lamprey genome does contain a single gene, somewhat related to Factor X and Factor V, but not identical to either. As the paper’s authors put it: “In summary, the genomic picture presented here suggests that lampreys have a simpler clotting scheme than later diverging vertebrates. In particular, they appear to lack the equivalents of factors VIII (or V) and IX, suggesting that the gene duplication leading to these factors, synchronous or not, occurred after their divergence from other vertebrates.” [p. 195]. To make things even worse for Luskin’s “core,” a previous study from Doolittle’s lab [Jiang & Doolittle, 2003] had already shown that the bits and pieces (protein domains) of most of the clotting factor proteins are present in a primitive, invertebrate chordate. This is exactly what one would expect from an evolutionary trajectory leading to the current system in vertebrates — the assembly of a complex pathway from pre-existing parts. [14]

Burges wrote his article in 2000, well before the Kitzmiller vs. Dover trial in 2005 in which Behe’s credibility on intelligent design was irretrievably tarnished. However, damning reviews were available before his article appeared in the Testimony, leaving one to wonder how comprehensively he researched his subject before writing.

3. The other examples of 'irreducible are also readily explained by evolution

The other examples of ‘irreducible complexity’ Burges cited have likewise proven to be anything other than challenges to modern evolutionary biology. The basal body of the flagellum is quite similar to the Type III secretion system which is used by some bacteria to inject toxins into cells:

Stated directly, the TTSS does its dirty work using a handful of proteins from the base of the flagellum. From the evolutionary point of view, this relationship is hardly surprising. In fact, it's to be expected that the opportunism of evolutionary processes would mix and match proteins to produce new and novel functions. According to the doctrine of irreducible complexity, however, this should not be possible. If the flagellum is indeed irreducibly complex, then removing just one part, let alone 10 or 15, should render what remains "by definition nonfunctional." Yet the TTSS is indeed fully-functional, even though it is missing most of the parts of the flagellum. The TTSS may be bad news for us, but for the bacteria that possess it, it is a truly valuable biochemical machine. 

The existence of the TTSS in a wide variety of bacteria demonstrates that a small portion of the "irreducibly complex" flagellum can indeed carry out an important biological function. Since such a function is clearly favored by natural selection, the contention that the flagellum must be fully-assembled before any of its component parts can be useful is obviously incorrect. What this means is that the argument for intelligent design of the flagellum has failed. [15]

Long an icon of the intelligent design community, the bacterial flagellum simply does not pose any conceptual problems for mainstream biology. When one examines the subject, it is painfully obvious that the special creationists know little about the flagellum. In fact, there is no such thing as “the” flagellum. Instead, there are many bacterial flagella with marked variation in form and function:

The most well-studied bacterial flagellar system is that of Salmonella enterica serovar Typhimurium (Salmonella typhimurium). However, in Gram positive bacteria, flagella lack P- and L-rings, and in spirochaetes the flagellar filaments rotate inside the periplasm. Some flagella rotate using proton-motive force, others depend on a sodium-ion gradient. In Sinorhizobium meliloti and Rhodobacter sphaeroides, the flagellum rotates unidirectionally, with a fast, slow or stop mechanism, whereas in S. typhimurium reversals in the direction of flagellar rotation are used to re-orientate the cell. Flagellar filaments vary in their physical properties: some show right-handed helical packing, others left-handed; some are flexible, others rigid; some are straight, others curly; some undergo post-translational modifications such as glycosylation or methylation, others do not. In Escherichia coli alone there are over forty antigenically distinct flagellins, with good evidence that variation is driven by diversifying natural selection. Indeed, flagellins in general provide a perfect illustration of Darwin’s dictum that “nature is prodigal in variety, though niggard in innovation”, in that the surface-exposed domains are highly variable, ranging in length from effectively zero to 800 residues, yet the peripheral domains that mediate inter-subunit interactions are highly conserved. Furthermore, some systems deploy a single flagellin, whereas others, like the S. typhimurium model system, exploit two different flagellins, but never in the same filament. In other exceptional cases, up to six different flagellins are incorporated into a single flagellum.

Many new flagellar systems have been discovered through genome sequencing — a trend that is likely to increase with time. For example, over three hundred flagellin sequences were obtained in a single sequencing project that focused on samples from the Sargasso Sea. By even the most conservative estimate, there must therefore be thousands of different bacterial flagellar systems, perhaps even millions. Therefore, there is no point discussing the creation or ID of ‘the’ bacterial flagellum. Instead, one is faced with two options: either there were thousands or even millions of individual creation events, which strains Occam’s razor to breaking point, or one has to accept that all the highly diverse contemporary flagellar systems have evolved from a common ancestor. [16]

The immune system and the vertebrate eye likewise pose no essential problems to mainstream science, despite Burges’ assertion that they are “irreducibly complex.” When he asserts:

At the end of the day, evolutionists are forced to maintain that such complexity arose in small steps even though they have absolutely no idea how this could have happened. It is simply a position of faith.[17]

he is simply wrong. Mainstream biology has made huge inroads into these problems such as the evolution of the immune system [18-20] and the vertebrate eye [21-23] to name two examples. One again comes back to the central problem that special creationists have simply failed to recognise that evolution refers not only to the theory to explain evolutionary change, and the evidence for evolution (common descent and large-scale evolutionary change). Unsolved problems in this field do not invalidate the overwhelming evidence that evolution has occurred, and it reflects badly on Burges that he fails to appreciate this fact.

4. Burges failed to inform his readers that Darwin's Black Box was not properly reviewed

A book as revolutionary in its goals as Darwin's Black Box should have been subjected to considerable scientific review prior to publication. This was not the case. While the scientific peer review process is not perfect, it does serve as a degree of quality control before papers are published in the literature. Therefore, any paper that makes it into the primary literature has at least been reviewed by senior scientists working in the field who will ensure that the paper is not the work of a crank, or makes basic errors of fact.

Curiously, Behe did not advance his thesis in the primary literature, choosing instead to bypass it and publish it in a book aimed at a popular audience. Despite this, he is on record as maintaining that his book had received a more thorough peer review than articles in the primary literature. This claim is impossible to reconcile with what four of these reviewers have stated.

Behe’s book referred to Doolittle’s work on blood clotting when making his assertion that the vertebrate blood coagulation cascade was “irreducibly complex”. Doolittle is a recognised authority in this area, and therefore his opinion was sought when the book was initially reviewed prior to publication. K. John Morrow, another person who initially reviewed the book sought Doolittle’s opinion on the part of Behe’s book that touched on his area of expertise. His opinion [24] was scathing:

November 14, 1995 

Professor K. John Morrow, Jr.
Dept. Cell Biology & Biochemistry
School of Medicine
Texas Tech University Health Sciences Center 3601
4th Street Lubbock, TX 79430
Dear Dr. Morrow, 

I read the draft of the chapter for a proposed book by Michael Behe that you sent me. As you warned me on the telephone, my own writings play a prominent role in his attack on evolution. I don't know whether the word ingenious or disingenuous is more appropriate here, but he has certainly turned all my thinking completely around to suit his own ends. That it is really disingenuous is clear from the fact that he has managed to belittle important scientific findings by couching them with sarcasm. 

But what annoyed me the most in the chapter was the author's appeal to Rube Goldberg, one of my favorite cartoonists, and a person I often refer to for my own perspective. On numerous occasions I have shown the two enclosed Goldberg cartoons as examples of how evolution works! Indeed, I used them in (trying to) teach our medical students about how complicated cascades work in contemporary cells. Also, I have used the same cartoons in debating our local creationist (Duane Gish), pointing out that certainly no Creator would have designed such a circuitous and contrived system. Instead, this is how the opportunistic hand of natural selection works, using whatever happens to be available at the moment. (I wonder if he knew about this?) 

But let me back up a bit. First, the 1993 article of mine, which is so heavily quoted from and intentionally disparaged, was the text of a lecture I presented at an international conference on blood clotting. It was presented to an audience of mainly clinicians and biotechnologists, not persons well versed in the rudiments of protein evolution. The tone was intentionally light and breezy. My "casual language" has to be viewed in this light. My main point was to demonstrate that the delicate balance of forward and backward reactions that regulate blood clotting came about in a step-by-step process. I emphasized that the Yin-Yang was simply a metaphor and that other similar point and counterpoint comparisons could be made. 

A more rigorous development of these ideas can be found in the cited references, one of which (Doolittle & Feng, 1987) is enclosed. This article predicted that certain components of the cascade appear relatively late in vertebrate evolution, and data in support of this contention are just now forthcoming (lower vertebrates appear to lack the equivalents of factors XI and XII). 

A wonderful example of how gene duplications operate in this regard was noted almost 25 years ago. Thus, in hemoglobin, similar sequence extrapolations backwards in time suggested that the gene duplication leading to alpha and beta chains occurred at about the time of the diversification of fishes (see Fig. 1 of Doolittle, 1987, (enclosed). Indeed, when hemoglobin from lampreys and hagfish were examined, they were found to be single-\|chained! They had diverged before the key alpha /beta duplication that has led to the allosteric regulation of oxygen transport. Max Perutz has written elegantly about this. 

Here are a few of his comments that I found most irritating. 

On page IV-29 the author bold-facedly claims that "the (Doolittle) article does not explain.. how clotting might have originated and subsequently evolved." and then in italics "..no one on earth has the vaguest idea how the coagulation cascade came to be." 

I disagree. I have a good idea, shared by most workers in the field, and it is a matter of the (important) details that we are trying to establish. 

On page IV-24, Behe underscores that no "causative factors are cited." "What exactly is causing all this springing and unleashing?" Gene duplications, of course, the frequency of which is difficult to measure (I often note that "duplication begets more duplication," for reasons of the misalignment of similar sequences), but which is turning out to be enormously more common than expected. 

Causation is tricky. Sometimes environmental or internal benefits are obvious. Often however, the rule for survival is "no harm, no foul," with adaptations occurring subsequently. For the moment, they don't even have to be slightly improved. 

As for the "enormous luck needed", we are now into the crux of all evolutionary problems, which is to say, what is the probability of survival? Population geneticists are attempting to answer such questions in general terms (see, e.g., J. B. Walsh, Genetics, 139, 421-428, 1995). In fact, the product of most gene duplications, which are the heart of the evolutionary process, are doomed to random oblivion (see enclosed, Doolittle, Science, 1981). 

Also, on page IV-26, he states, "the crucial issues of how much? how fast? when? where?" are not addressed. These are relevant and not unknowable matters. There is a wonderful article about to appear in Molecular Phylogenetics by D. Gumucio et al on how fetal hemoglobin has evolved in primates and that also outlines exactly the regulatory circumstances that allow its differential expression. Finally, my "model" does give some important numbers. The power of sequence-based analysis is that it reveals the order of appearance of new proteins, even when the sequences are limited to one or a few species. As noted above, it also has the power to make predictions about the occurrence of proteins in different creatures. 

In the meantime, we must ask Mr. Behe whether he doubts the existence of gene duplications? (There are many examples of closely related species where one has n copies of a gene and the other m.) If he acknowledges their existence, then how does he account for the pseudogenes that these duplications often give rise to? Does he think they have a function? And what does he think was the origin of allosteric hemoglobins in all but the most primitive vertebrates? As I say, even his derisive comments call attention to a system that could only have come about by natural selection. 

Should the book be published? Scurrilous as it is, I am a believer in a free press. I also know most publishers will publish anything that can make money, and I'm sure there's a naive market for claptrap like this. 

I only ask that if you do recommend publication that you suggest that I be invited to review the book, so I can put my own Rube Goldberg cartoons to use. 

Feel free to phone if there are other questions. 

Sincerely, 

Russell F. Doolittle

Research Professor

of Biology and Chemistry

Doolittle’s review of Darwin’s Black box in the Boston Review was equally savage:

In Darwin's Black Box, Michael Behe has concluded that blood clotting--Behe's "favorite pathway," as Allen Orr puts it--is simply "too complex to have evolved." Worse, he has taken one of my own articles to illustrate his view. The article was the text of a 1993 lecture presented at an international conference on blood clotting. It was one of a series of talks that were billed as "state of the art" and presented to an audience of mainly clinicians and biotechnologists. Because the audience was hardly conversant in the facts of evolution, my tone was intentionally light and breezy, and my language was casual. The main point was to demonstrate that the delicate balance of forward and reverse reactions that regulate blood clotting came about in a step-by-step fashion. I summarized events with the metaphor of Yin and Yang, and emphasized that other similar point-and-counterpoint comparisons could be made. 

But Behe had a ball with Yin and Yang. While reminding readers over and again that this was a "state of the art" article, he accuses me of "imagining" the evolution of blood clotting and "papering over the dilemma [of the irreducibly complex] with a hail of metaphorical references to yin and yang." He ridicules the whole thing as a "Calvin and Hobbes" creation. He concludes that "no one on earth has the vaguest idea how the coagulation cascade came to be." 

I beg to differ. In recent years an enormous amount of evidence has been accumulated about the evolution of blood clotting, and it overwhelmingly supports the suggestions made in my graduate essay. [25]

Any paper submitted to a reputable journal that made similar claims about vertebrate blood coagulation would not have made it past peer review. Doolittle’s scathing review of the book, as well as the results of its ‘peer review’ prior to publication by the same author alone cast grave doubts on its scientific integrity.

Another reviewer was Michael Atchison, head of biochemistry at the University of Pennsylvania veterinary school. Atchison is a Christian, and is sympathetic to Behe’s argument. He is also on record as stating that his ‘peer review’ was a ten minute discussion of the book from the publisher via telephone:

While I was identifying myself as a Christian in Philadelphia, a Biochemist named Michael Behe at Lehigh University was writing a book on evolution. As a Biochemist, Behe found the evidence for Darwinian evolution to be very thin. In fact, when he looked at the cell from a biochemical perspective, he believed there was evidence of intelligent design. Behe sent his completed manuscript to The Free Press publishers for consideration. The editor was not certain that this manuscript was a good risk for publication. There were clearly theological issues at hand, and he was under the impression that these issues would be poorly received by the scientific community. If the tenets of Darwinian evolution were completely accepted by science, who would be interested in buying the book? 

]The editor shared his concerns with his wife. His wife was a student in my class. She advised her husband to give me a call. So, unaware of all this, I received a phone call from the publisher in New York. We spent approximately 10 minutes on the phone. After hearing a description of the work, I suggested that the editor should seriously consider publishing the manuscript. I told him that the origin of life issue was still up in the air. It sounded like this Behe fellow might have some good ideas, although I could not be certain since I had never seen the manuscript. We hung up and I never thought about it again. At least until two years later. 

After some time Behe's book Darwin's Black Box (The Free Press, 1996) was published. It became an instant best-seller and was widely acclaimed in the news media. It is currently in its 15th printing and over 40,000 copies have been sold. I heard about it, but could not remember if this was the same book that I received the call about from the publisher. Could it be? In November 1998, I finally met Michael Behe when he visited Penn for a Faculty Outreach talk. He told me that yes, indeed, it was his book that the publisher called me about. In fact, he said my comments were the deciding factor in convincing the publisher to go ahead with the book. [26]

Listening to a ten minute précis of a book that one has not read is not peer review, and the fact that this ‘review’ was instrumental in the book being published is telling, particularly given the withering criticism it received from those who did read it.

One of Behe's reviewers who did see the book when he reviewed it is the molecular biologist K. John Morrow who notes that:

"I did review Behe's book for a publisher who, if I recall correctly, turned it down on the basis of my comments, and those of others (including Russell Doolittle who trashed it). When I reviewed Behe's book I was much more polite than Doolittle, who didn't mince words. Eventually Behe found another publisher, so he's right; it was peer reviewed. What he doesn't say is that is was rejected by the first set of reviewers. 

"I also debated Behe in Dallas in 1992. Once, again, I attempted to be civil, professional and dignified. Behe's response was aggressive, condescending and simply rude. 

"I will say, unequivocally, I am (as practically every professional working biologist I have ever met) convinced by the overwhelming body of evidence that Darwin's concept of evolution, and its subsequent modifications by the last 150 years of investigation, is the correct, and the best explanation for the great cornucopia of living creatures with which we share this planet. 

"I'm absolutely appalled by Behe's arguments, which are simply a rehash of ideas that Darwin considered and rejected. There is not a shred of evidence to support intelligent design, and a vast body of evidence that argues against it. It is not a scientific hypothesis, it is simply the philosophical wanderings of an uniformed (or disingenuous) mind. 

"At present I'm involved in product development for an immunodiagnostics company, and we are discussing how to approach to Avian flu, and how we can design a test that takes into account the constantly evolving nature of the RNA viruses. Do the intelligent designers want to return us to a time when mankind attributed disease to evil spirits, and allow us no tools to understand the ravages of epidemic diseases, and how to design therapies and diagnostics against them? 

"I believe that the argument is not about science at all, but simply right wing fundamentalists using a different tactic to force religious teaching in the public schools. I thought that Judge Overton had put this case to rest 30 years ago, but apparently not. 

"Thanks for this opportunity to clarify my feelings on this subject. [27]

It is difficult to reconcile this with Behe's claim that his book was reviewed far more rigorously than a typical manuscript as he asserted during the Kitzmiller vs. Dover trial. The trial transcript noted the following:

Q. You would agree that peer review for a book published in the Trade Press is not as rigorous as the peer review process for the leading scientific journals, would you? 

A. No, I would not agree with that. The review process that the book went through is analogous to peer review in the literature, because the manuscript was sent out to scientists for their careful reading. 

Furthermore, the book was sent out to more scientists than typically review a manuscript. In the typical case, a manuscript that's going to -- that is submitted for a publication in a scientific journal is reviewed just by two reviewers. My book was sent out to five reviewers. 

Furthermore, they read it more carefully than most scientists read typical manuscripts that they get to review because they realized that this was a controversial topic. So I think, in fact, my book received much more scrutiny and much more review before publication than the great majority of scientific journal articles. [28]

The withering review by Doolittle alone would have sunk the book if it had been subjected to more detailed scrutiny than a ten minute phone call. It was disingenuous of Behe to claim that his book received more review before publication than most articles.

If Behe’s book had cited peer-reviewed evidence for intelligent design in his book, one may have been a little more forgiving. However, when under oath, Behe admitted that there was no peer-reviewed evidence for intelligent design:

The evidence presented in this case demonstrates that ID is not supported by any peer-reviewed research, data or publications. Both Drs. Padian and Forrest testified that recent literature reviews of scientific and medical-electronic databases disclosed no studies supporting a biological concept of ID...On cross-examination, Professor Behe admitted that: “There are no peer reviewed articles by anyone advocating for intelligent design supported by pertinent experiments or calculations which provide detailed rigorous accounts of how intelligent design of any biological system occurred.”…Additionally, Professor Behe conceded that there are no peer-reviewed papers supporting his claims that complex molecular systems, like the bacterial flagellum, the blood-clotting cascade, and the immune system, were intelligently designed…In that regard, there are no peer-reviewed articles supporting Professor Behe's argument that certain complex molecular structures are "irreducibly complex."…. In addition to failing to produce papers in peer-reviewed journals, ID also features no scientific research or testing. [29]

Those who read Behe’s book – particularly those qualified in a field of relevance to the book – were scathing in their criticism of the book’s shortcoming. One sympathetic reviewer openly admitted that he never read the book, but instead listened to a ten minute summary of it over the telephone. Behe however claimed that his book had received 'much more scrutiny and much more review' than most papers received, a claim extremely difficult to reconcile with what has been detailed above. Tellingly, when asked whether there was any peer-reviewed evidence for his thesis, he answered in the negative. Any open minded person interested in Behe's claims would have easily found out just how poorly this book was received, and avoided it accordingly.

Unfortunately, Burges never once tells his readers that Behe's book had not been properly reviewed prior to publication, and in fact had been subjected to withering criticism by experts in areas of direct relevance to the book's argument. For a science editor of a major Christadelphian magazine to confidently state that "this book is strongly recommended, especially for young Christadelphians considering the study of life sciences at advanced or degree level" is outrageous. None of this information would have been hard to find for a science editor who had properly reviewed the book instead of uncritically recommending something to provide a pseudoscientific veneer to his special creationism.

5. Burges' sole attempt to engage with critics of Behe shows that he has missed the point

The only time Burges even attempts to engage with Behe's critics comes near the end of the book:

His critics have claimed that nature in fact operates a system of ‘redundant complexity’. This is based upon the knowledge that many enzymes have multiple functions, and, in some cases, if one enzyme is absent another will take over its role. Thus it is surmised that new mechanisms evolved by co-opting enzymes already being used for other, existing pathways. But the same facts can be used to argue that, just as a human engineer might include backup systems when designing a critical piece of equipment, so God, the Great Designer, has deliberately built such redundant complexity into biochemical systems in order to make them more robust. [30]

The analogy with redundant engineering systems shows that Burges simply has not got the point. New functions can arise when a gene that codes for a molecular receptor or hormone is duplicated. This new gene is not needed, so is free to mutate and acquire new functions. This is not the same thing as redundant systems, where multiple parallel sub-systems already exist, ensuring that if one sub-system fails, a backup unit can take over.

We have ample evidence that complex systems can evolve by a process of gene duplication and mutation. Joe Thornton and his colleagues have been researching the evolution of steroid hormones for some time:

Here we demonstrate how an integrated molecular system—the specific functional interaction between the steroid hormone aldosterone and its partner the mineralocorticoid receptor—evolved by a stepwise Darwinian process. Using ancestral gene resurrection, we show that, long before the hormone evolved, the receptor's affinity for aldosterone was present as a structural by-product of its partnership with chemically similar, more ancient ligands. Introducing two amino acid changes into the ancestral sequence recapitulates the evolution of present-day receptor specificity. Our results indicate that tight interactions can evolve by molecular exploitation—recruitment of an older molecule, previously constrained for a different role, into a new functional complex. [31]

Behe's assertions that cumulative change cannot evolve complexity, and that some structures are 'irreducibly complex' are baseless. It reflects poorly on the credibility of the Testimony magazine that such an uncritical, scientifically uninformed review was ever published.

This article includes material first published at BEREA Portal and is used with permission

References

1. Behe M Darwin's Black Box: The Biochemical Challenge to Evolution (1996: Free Press)

2. Burges D "The biochemical challenge to evolution" The Testimony (2000) 70:93-94

3. Miller, KR. (1996). "Darwin's Black Box, reviewed by Kenneth R. Miller". Creation/Evolution 16: 36–40.

4.  Dorit, R (1997). "A review of Darwin's Black Box". American Scientist September/October 1997.

5. Coyne, J.A. (1996). "Darwin's Black Box: The Biochemical Challenge to Evolution by MJ Behe". Nature 383 (6597): 227

6. Orr, H.A (December 1996/January 1997). "Darwin v. Intelligent Design (Again): The latest attack on evolution is cleverly argued, biologically informed—and wrong". Boston Review 22:(6)
7.  Muller, H. J. (1918) "Genetic variability, twin hybrids and constant hybrids, in a case of balanced lethal factors." Genetics 3:422-499
8.  Miller K “Smoke and Mirrors, Whales and Lampreys: A Guest Post by Ken Miller” The Loom Jan 2 2009
9.  Jiang Y, Doolittle RF The evolution of vertebrate blood coagulation as viewed from a comparison of puffer fish and sea squirt genomes (2003) Proc. Natl. Acad. Sci. USA100, 7527-7532
10. ibid, p 7527
11. loc cit
12. ibid, p 7531-7532
13, See ref 8.
14. See ref 8.
15. Miller K "The Flagellum Unspun - The Collapse of Irreducible Complexity"
16.  Pallen MJ, Matzke NJ (October 2006). “From the Origin of Species to the origin of bacterial flagella”. Nat Rev Microbiol. 4 (10): 784–90.
17. Burges p 94
18. Agrawal A et al “Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system” Nature 394, 744-751 (20 August 1998)
19. Sackton TB et al “Dynamic evolution of the innate immune system in Drosophila” Nature Genetics 39, 1461 - 1468 (2007)
20. Martin F. Flajnik MF, Kasahara M Origin and evolution of the adaptive immune system: genetic events and selective pressures Nature Reviews Genetics 11, 47-59 (January 2010)
21. Oakley TH, Pankey MS Opening the “Black Box” The Genetic and Biochemical Basis of Eye Evolution Evo Edu Outreach (2008) 1:390-402
22. Piatigorsky J A Genetic Perspective on Eye Evolution: Gene Sharing, Convergence and Parallelism Evo Edu Outreach (2008) 1:403-414
23. Lamb TD, Collin SP, Pugh EN Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup Nature Reviews Neuroscience 8, 960-976 (December 2007) 
24. Brayton E “Two of Behe’s Reviewers Speak Out” Dispatches From the Culture Wars October 27, 2005. http://scienceblogs....ers_speak_o.php
25. Doolittle, Russell “A Delicate Balance” Boston Review (March/February 1997)
26. Atchinson M “Mustard Seeds” http://www.leaderu.com/real/ri9902/atchison.html
27. See ref. 24.
28. Kitzmiller v. Dover Area School District Trial transcript: Day 12 (October 19), AM Session, Part 1
29. Kitzmiller v. Dover Area School District/4:Whether ID is Science, p88
30. Burges p 94
31. Jamie T. Bridgham, Sean M. Carroll, Joseph W. Thornton "Evolution of Hormone-Receptor Complexity by Molecular Exploitation" Science (2006) 312: 97-101