Kenneth Miller's Best Arguments

Against Intelligent Design

Sean D. Pitman, M.D.

© May, 2007

       Kenneth Miller (born 1948) is a professor of biology at Brown University. He received his Sc.B. in Biology from Brown University in 1970 and Ph.D. in Biology from the University of Colorado in 1974. His research involved problems of structure and function in biological membranes.

        Although Miller is a devout Catholic, he is an outspoken opponent of creationism as well as supporters of the intelligent design movement.  He has written a popular book (published in 2000) on the topic entitled, "Finding Darwin's God: A Scientist's Search for Common Ground Between God and Evolution" in which he argues that belief in both God and evolution are not mutually exclusive notions. It is just that belief in God is based on "faith" while belief in evolution is based on "science".  

        As an aside, Kenneth Miller does describe himself as a "creationist" in a certain sense because of his belief in God and the position that God has played some part in the development of the universe and in various interactions with mankind. However, Miller says that this belief is independent of science and is based entirely on his religious faith.  How ones faith, independent of any scientific investigation or physical testability, can produce meaningful "truths", such as the notion that God is in any way relevant to anything that happens or has happened in the physical universe, is not quite clear from Miller's book or subsequent statements. In fact, Miller argues that, "Whether God exists or not is not a scientific question" (NOVA Link). This is one of the reasons why those like Richard Dawkins are so frustrated with those who still cling to what he calls "The God Delusion" without any real solid scientific testable evidence for the very existence of God via his interaction with humans or the physical universe in any way. Given Miller's arguments in this regard, I certainly do sympathize with Dawkins and think that at least Dawkins is being far more rational in his thinking than is Miller and other scientists who suggest that science and faith are completely different yet equally valid means of approaching "truth".  With Dawkins, I fail to see the significant difference between Miller's "faith" and "wishful thinking"? - like a child's belief in Santa Claus.

        In any case, Miller has appeared in court as a witness and on panels debating the teaching of intelligent design in schools. In 2002, the Ohio State Board of Education held a public debate between prominent evolutionists, including Miller, and proponents of intelligent design.  He was a witness in Selman v. Cobb County, testing the legality of stickers calling evolution a "theory, not a fact" that were placed on the biology textbook Miller authored. In 2005, the judge ruled that the stickers violated the Establishment Clause of the First Amendment to the United States Constitution – the decision was vacated on appeal, and was remanded back to the lower court and was eventually settled out of court. Miller was also the plaintiff's lead expert witness in the Kitzmiller v. Dover Area School District, challenging the school board's mandate to incorporate intelligent design into the curriculum. The judge in that case also ruled decisively in favor of the plaintiffs.

Before reading further it might be most effective to review a very interesting video of Miller's Lecture at Case Western University dealing with this topic:

Irreducible Complexity

        Perhaps one of the biggest challenges to the modern theory of evolution, or at least a challenge that has created a fair bit of discussion within the scientific community, is a concept known as "irreducible complexity" - originally developed by Michael Behe in his 1996 book "Darwin's Black Box".  Behe, professor of biochemistry at Lehigh University, boldly claims that,  “Molecular evolution is not based on scientific authority.  There is no publication in the scientific literature in prestigious journals, specialty journals, or books that describe how molecular evolution of any real, complex, biochemical system either did occur or even might have occurred.  There are assertions that such evolution occurred, but absolutely none are supported by pertinent experiments or calculations.” ¹  

        Since the publishing of Behe’s book a fair bit of controversy has arisen over such statements. Surprisingly, many evolutionary scientists seem to grudgingly agree with Behe, at least in some limited way.  For example, microbiologist James Shapiro of the University of Chicago declared in National Review that, "There are no detailed Darwinian accounts for the evolution of any fundamental biochemical or cellular system, only a variety of wishful speculations" (Shapiro 1996).  In Nature, University of Chicago evolutionary biologist, Jerry Coyne, noted that, "There is no doubt that the pathways described by Behe are dauntingly complex, and their evolution will be hard to unravel. . . . [W]e may forever be unable to envisage the first proto-pathways" (Coyne 1996).  In Trends in Ecology and Evolution Tom Cavalier-Smith, an evolutionary biologist at the University of British Columbia, wrote, "For none of the cases mentioned by Behe is there yet a comprehensive and detailed explanation of the probable steps in the evolution of the observed complexity. The problems have indeed been sorely neglected--though Behe repeatedly exaggerates this neglect with such hyperboles as 'an eerie and complete silence'" (Cavalier-Smith 1997).  Evolutionary biologist, Andrew Pomiankowski, agreed. In New Scientist, he challenged anyone to, "Pick up any biochemistry textbook, and you will find perhaps two or three references to evolution. Turn to one of these and you will be lucky to find anything better than 'evolution selects the fittest molecules for their biological function'" (Pomiankowski 1996). In American Scientist, Yale molecular biologist, Robert Dorit, suggested that, "In a narrow sense, Behe is correct when he argues that we do not yet fully understand the evolution of the flagellar motor or the blood clotting cascade" (Dorit 1997).

        There are many examples of what Behe describes as irreducibly complex biosystems.  However, the most famous of these is likely the bacterial flagellar motility system.  The flagellum is so famous and so commonly used by intelligent design advocates that Miller refers to it as the "poster child" of the intelligent design movement - and rightly so. The flagellar motility system is quite impressive indeed.  Consider that the flagellar system, in particular, requires the services of about 50 genes - including the genes for the sensory apparatus (turns the flagellum clockwise or counterclockwise at a greater or lesser rate depending on the environment) and the genes needed to code for proteins that assist in building the flagellum (about 40 structural proteins total).  The total number of fairly specified (specifically arranged for minimum function) codons of DNA needed to code for the flagellar motility system, at minimum, is well over 10,000 codons.  That's like a good-sized 2,000-word essay.  Without this minimum in place, in its entirety, the motility function of the flagellum cannot be realized to any useful degree of functionality.  In short, when it comes to the producing flagellar motility, a sizable minimum structural threshold is required and this requirement is "irreducible" if one wishes to maintain flagellar motility.  

        It is Behe's argument that such a high-threshold function cannot be built up by evolutionary mechanisms of random mutation and natural selection because it doesn't work at all until all of its many parts are in their proper place at the same time.  How can Nature get all of these parts together gradually? Miller counters by arguing that even highly complex functions, like the flagellum, are not really irreducibly complex since there are various subsets of the parts of such high-level systems that have various uniquely independent functions. Miller argues that if Behe were right, if one took away a part of the flagellum, the resulting structure could have no beneficial function whatsoever.  Therefore, if any beneficial subsystem function can be found, Behe's notion is clearly falsified - i.e., the system isn't really functionally "irreducible".

TTSS

        So, has Miller actually found a subsystem with a potentially beneficial function?  Obviously, he has - - or I wouldn't be writing this essay.  Miller points out that if not just one or two proteins are removed from the flagellar system, but 30 of the around 40 structural proteins are removed, one would expect, if Behe were right, that what would be left would be as functional as a pile of junk.  Yet, this isn't the case.  Take away 30 or so particular parts of a flagellum and what's left (~10 homologous proteins) is a functionally beneficial toxin injector system known as the Type Three Secretory System (TTSS).

        The TTSS system is actually used by certain kinds of disease-causing bacteria known as gram-negative pathogens that attack plants and animals.  Obviously the TTSS system is quite beneficial to certain types of pathogenic bacteria. It is indeed a true survival/reproductive advantage to those bacteria that have and use it. Therefore, it seems quite reasonable that the TTSS system could be used as a viable stepping stone along the pathway toward the higher-level flagellar motility system.  And presto, Miller has just devastated Behe's notion of irreducibly complexity.  This is in fact one of the main points brought up to challenge Behe at the Dover trial.  And, it certainly did seem to convince a great many people, including the presiding judge.  What wasn't presented about at the trial though, or in the recent NOVA report on the trial (aired November 13, 2007), is an interesting question: 

        Given Miller's position as correct, which system is likely to have evolved first - - the much simpler TTSS system or the much more complex flagellar motility system?  Given Miller's argument, it seems intuitively obvious that the TTSS system should evolve first followed by the more complex flagellar system - right?  Of course . . .

        It is strange, then, that the TTSS system is thought to have evolved hundreds of millions of years after flagellar evolution. That's right. Many scientists believe that there is very good evidence to believe that the TTSS system arose from the fully formed flagellum - - not the other way round.  Consider that the bacterial flagellum is found in mesophilic, thermophilic, gram-positive, gram-negative, and spirochete bacteria while TTSS systems are restricted to a few gram-negative bacteria. Not only are TTSS systems restricted to gram-negative bacteria, but also to pathogenic gram-negative bacteria that specifically attack animals and plants . . . which supposedly evolved hundreds of millions of years after flagellar motility had already evolved.  Beyond this, when TTSS genes are found in the chromosomes of bacteria, their GC (guanine/cytosine) content is typically lower than the GC content of the surrounding genome. Given the fact that TTSS genes are commonly found on large virulence plasmids (which can be easily passed around between different bacteria), this is good evidence for horizontal transfer to explain TTSS gene distribution.  Flagellar genes, on the other hand, are usually split into 14 or so operons, they are not found on plasmids, and their GC content is the same as the surrounding genome suggesting that the code for the flagellum has not been spread around by horizontal transfer. Additional evidence for this comes from the fact that the TTSS system shows little homology with any other bacterial transport system (at least 4 major ones). Yet, evolution is supposed to build upon what already exists.  Since the TTSS system is the most complex of the bunch, why didn't it evolve from one of these less complex systems and therefore maintain some higher degree of homology with at least one of them? This evidence suggests that the TTSS system did not exist, nor anything homologous, in the "pre-flagellar era".  It must therefore have arisen from the fully formed flagellum via the removal of pre-existing parts - and not the other way around. In fact, several scientists have actually started promoting this idea in recent literature.^3-8

        Now, isn't that just most interesting? - totally unpredictable based on Miller's arguments.  Rather, it seems much more in line with the predictions of intelligent design; that what is more functionally complex can indeed degenerate into something that has fewer structural requirements.  But, is it just as easy to turn things around and go upstream; so to speak?  Not at all.  In other words, it is far easier to destroy a car's motility function and still have its headlights work than to go the other way around and get the motility function starting with working headlights.  Yet, you won't hear this little interesting fact in Miller's books or lectures.  It certainly wasn't brought up by NOVA in their coverage of the Dover trial.  Even though the experts presented know of this fact, they probably don't want to present it for fear of confusing their intended audience.

But the Lights Still Work!

        In short, what's wrong with Miller's argument is that the motility function of the bacterial flagellum does indeed require a certain rather large number of specifically arranged amino acid residue "parts" as well as the underlying codes in DNA.  Without all of these parts in place, in their proper order, at the same time, the motility function cannot be realized at all - not even a little bit.  Reduce the number of parts below this minimum threshold limitation and the motility function simply disappears - poof.  Like turning out a light.  The fact that various subsystems might still maintain their own separate function does not mean that the minimum structural requirements needed for the motility function of a bacterial flagellum is therefore significantly reducible.  It certainly is not.  The same thing is true about the motility function of a car.  Just because the lights and CD player might still work without the drive shaft doesn't mean the car's motility function is therefore "reducible".  It isn't. To suggest otherwise, as Miller and many other scientists do and as NOVA did, is simply a misdirect - a misdirect which is a seemingly deliberate misdirect. 

        However, to help Miller out of a bit of a pickle here, just because a function requires a certain minimum structural threshold does not mean that it is necessarily unevolvable. This is perhaps where Behe could be more clear. Behe seems to indicate in his books and lectures that only certain types of biosystems are "irreducibly complex".  That's simply not true. It seems like all functional systems have minimum structural threshold requirements and therefore all are "irreducibly complex".  And, many types of these irreducible beneficially functional systems are actually evolvable.  Irreducible complexity does not automatically mean that a system cannot be evolved via random mutation and natural selection - despite Behe's apparent claims to the contrary.  If the next closest beneficial subsystem just so happens to be one or two residue changes or mutations away from a given starting point, the odds are extremely good that such an evolutionary step will be taken in very short order by a colony of just a few million bacteria (i.e., in one or two generations to cover such a small non-beneficial gap distance).  And, when it comes to many types of functional systems, such evolution does happen - and quickly (a few examples are discussed in some detail below).  

        The problem is that the proposed evolutionary mechanism of random mutation and function-based selection (i.e., Natural Selection) starts to stall out, in an exponential manner, with each step up the ladder of minimum structural threshold requirements.  While there are many examples of evolution in action producing novel systems of function that require dozens to a few hundred fairly specified amino acid residues, there are no examples of evolution in action (i.e., examples that can actually be observed in real time) beyond the 1,000aa threshold. There isn't a single example of such evolution in all of scientific literature - not one example.  

        What is the reason for this stalling out effect? for this "limited evolutionary potential" where evolution happens very quickly for low-level functional systems, less quickly or often for higher-level systems, and not at all beyond the 1,000aa structural threshold?  Well, it seems as though the average distance (as a Poisson distribution) between what exists in a gene pool and what might exist to some benefit within the vastness of the potential of sequence space grows in a linear manner with each increase in the minimum structural threshold requirements of different types of functional systems.  Those types of systems that have greater minimum structural threshold requirements are more widely spaced, like islands in sequence space, from all other existing and potentially existing beneficial systems.  These higher-level islands are surrounded, on all sides, by non-beneficial sequences so that getting from one island to the next by random mutation requires a truly random walk or random selection process.  Nature cannot guide the series of mutations across this gap because nature only selects, in a positive manner, what works right now - not what might work in the future.  So, until a random mutation happens to land on a distant island by sheer luck, natural selection plays no part.  As it turns out, a linear increase in the non-beneficial gap size translates into an exponential increase in the average number of mutations (and time) necessary to cross the gap.  Well before the 1,000aa threshold is reached, the average time required to cross the expanding gap works its way into the trillions upon trillions of years - even given a population of bacteria the size of all the bacteria on Earth (calculation).

Examples of Evolution In Action

2,4-DNT

        Another argument forwarded by Kenneth Miller has to do with a very interesting paper by Johnson et. al. reporting on the very real evolution of a novel enzymatic biosystem known as 2,4-dinitrotoluene or 2,4-DNT.⁹  What is interesting here is that 2,4-DNT is a synthetic compound that was first synthesized in the 1930s and comprises one of the components of the famous explosive TNT as well as expanded polyurethane foam.  Johnson et. al. somehow noticed that certain types of bacteria in the surface water and soil of Radford Army Ammunition plant in West Virginia were actually eating or metabolizing 2,4-DNT.  The bacteria identified were Burkholderia cepacia R34, a strain that grew using 2,4-DNT as a sole carbon, energy, and nitrogen source. The genes in the evolved degradative pathway were identified within a 27 kb region of DNA.

        Now, what is most interesting is the way in which these bacteria achieved this feat.  They co-opted enzymes that were already present and working as parts of other enzymatic pathways to perform an entirely new type of function - i.e., the digestion or metabolism of 2,4-DNT.  As it turns out the 2,4-DNT pathway that evolved ultimately involved the use of seven different enzymes.  "Inferences from the comparison of the structural genes of the 2,4-DNT pathway suggest that the pathway came together from three sources."⁹ 

        Of the seven enzymes in the 2,4-DNT metabolism pathway four of the key enzymes include dntAaAbAcAd (745aa), dntB (548aa), dntD (314aa) and dntG (281aa).  Note that the first two steps (illustrated at the right - dntAaAbAcAd and dntB) produce the byproduct NO₂- (Nitrite)^..  As it turns out, nitrite can be used for energy by bacteria known as nitrifying bacteria.  And, you guessed it, Burkholderia cepacia are nitrifying bacteria.  Why is this important?  Because, it means that each one of the first two steps in the pathway are functionally beneficial since they both provide a source of additional energy to the bacteria that gain such enzymatic activities (see addendum).¹⁰  

        In addition, each of these steppingstones has independent function in that no specific arrangement or orientation is needed, relative to the other elements in the enzymatic cascade, before its own function can be realized. Statistically, this is very important because far less structural specificity is required before the next functional step can be realized - especially if a functionally equivalent enzyme already exists as part of any other system of function.  And, guess what, all of the parts in the 2,4-DNT cascade already existed, preformed, as parts of other systems of function within the bacterium.   

        If all the needed enzymes are already being made, as parts of other systems, then obviously not much change or evolution is required to be able to use the 2,4-DNT molecule for energy. Unlike bacterial motility systems, enzymatic cascades need not self-assemble themselves in any particular way before the function in question can be realized.  All that needs to happen is for all the required enzymes to be present somewhere in the intracellular environment (in any order/arrangement).  This is not the case for non-cascading functions (i.e., bacterial motility systems) where all the protein parts are required to be in a particular order (i.e., a particular three dimensional arrangement) all working together at the same time before the function in question will be realized.

        This is not to say that cascading systems have no significant functional complexity. Many of them are quite complex, but none are significantly more complex than their most complex single component part.  The most complex single part in the 2,4-DNT cascade seems to be the dntAaAbAcAd enzyme, which requires around 745 fairly specified amino acid residues.  Given just this degree of specificity alone, without the original genes and enzymes in place to begin with, even this relatively simple enzymatic function would most likely not have evolved.  The authors themselves state as much when they note that the "De novo evolution of genes for nitrotoluene degradation during the short period of time seems unlikely."⁹   

        Compare such cascading functional systems to a functional system like flagellar motility where all the parts are required to be in a very specific arrangement relative to all the other parts in the system to achieve the next beneficial steppingstone function. What this means is that the odds needed to get all the needed parts in the right order for a cascade are much much less than the odds needed to get all the right parts for a fully specified system of equal overall size.

        For example, if you needed 5 specific 3aa residues to form a certain cascading-type function, what are the odds that all 5 will exist within a pool of 1 billion different 3aa sequences?  Well, since there are only 8,000 possible 3aa sequences (20³), the odds that all 5 will exist preformed somewhere in the gene pool are very very good - much better than 99% chance. The calculated is as follows:

        The odds that one of the 3aa sequences will not appear in 8000 3aa characters is (7999/8000) = 0.999875 chance.  So, the odds that a specific 3aa sequence will appear in a group of 8000 3aa sequences is 1- 0.999875 = 0.000125.  Now, the odds that a specific 3aa sequence will not appear anywhere in our pool of 1 billion 3aa sequences is (7999/8000)^1.25e5 = ~1.63e-7.  So, the odds that one specific 3aa sequence will appear in our pool is 1 - 1.63e-7 =  0.9999998 . . .  And, the odds that all five 3aa sequences will exist in this pool somewhere are 0.9999998⁵ = 0.9999990. In other words, better than a 99.9% chance that all 5 needed parts will exist within a given genome.

        Now, compare this with the odds of achieving a system that requires all five specific 3aa sequences to be specifically arranged relative to each other.  The number of different specific sequences possible is at least 20¹⁵ = 32,768,000,000,000,000,000 (~3.3e19).  So, the odds that one particular 15aa arrangement will appear within a pool of just 1 billion different options is around 1 in 1e10 pools.¹¹
        See the difference?

Lactase and Nylonase

        Miller often uses actual examples of evolution in action in his lectures and books - like the evolution of novel nylonase and lactase enzymes.  While these most certainly are real examples of evolution in action, they are easily explained with the odds of evolvability being similar to those described above for the 2,4-DNT cascading system.  

        Let's start with the lactase example.  In his 1999 book, Finding Darwin’s God, one of Miller’s challenges of Behe’s position includes a research study from the early 80s carried out by professor Barry Hall, a biologist from the University of Rochester.  What Hall did was very interesting. He deleted a gene (lacZ) in a type of bacteria (E. coli) that makes a lactase enzyme (galactosidase).  This lactase enzyme converts a sugar called lactose into the sugars glucose and galactose.  E. coli then process glucose and galactose further to extract energy.  One might think that when Hall deleted the gene that codes for the lactase enzyme that these bacteria would never be able to use lactose for energy again.  However, when Hall exposed the mutant bacteria to lactose enriched growth media, that they quickly modified a different gene, which Hall named the "evolved ß-galactosidase gene" (ebg), to produce a pretty good lactase enzyme.  This is interesting because the original gene product did not have the lactase function.  Only after a key random mutation was this genetic sequence able to produce a protein with the lactase function.¹²  

Behe counters by arguing that as far as the active sites of the lac and ebg ß-galactosidase enzymes are concerned, that they are essentially the same with both being a part of a family of highly conserved ß-galactosidases - identical at 13 of 15 active-site amino acid residues.  The two mutations in the ebg  ß-galactosidase,  that increase its ability to hydrolyze lactose, change the two non-identical residues back to those of the other ß-galactosidases.  So, before the evolution of the lactase ability of the ebg gene, its active site was already a near duplicate of other ß-galactosidases.¹³

  Even so, this really was quite an amazing experiment in that a novel enzymatic function, which was not present in the entire gene pool prior random mutation and natural selection, did in fact evolve in real time.  According to Miller and Hall, and many others quoting the same or similar experiments, such experiments give demonstrable proof of the proposed evolutionary mechanism in action.  Obviously then, Behe does not know what he is talking about . . . or does he? Consider that fairly often things are not quite as they would appear at first glance.

Most descriptions of Hall's experiments end with E. coli evolving the lactase function back again.  This is very interesting because Hall's actual experiments did not end there.  After his initial success, Hall wondered if any other genes would be able to evolve the lactase function.  So, he deleted the ebg gene as well as the lacZ genes to test this hypothesis. And, something most interesting happened - nothing.  No new gene or portion of DNA evolved the lactase function despite tens of thousands of generations of time, a huge population size, high selection pressure, and a high mutation rate.  Now that is just fascinating . . .  Despite tens of thousands of generations with large population numbers and high mutation rates, no new lactase enzyme evolved. Hall himself noted in his paper that these double mutant bacteria seemed to have “limited evolutionary potential.”¹² 

Other unfortunate bacteria seem to be just as "limited" in their evolutionary potential. Even though they would significantly benefit, many types of bacteria, after more than a million generations, have not been observed to evolve a relatively simple lactase enzyme. This is fewer generations than it supposedly took humans to evolve from ape-like creatures. One should also note that these same bacteria, unable to evolve a lactase enzyme, are all able to evolve, in relatively short order, resistance to any antibiotic that comes their way. So what is it, exactly, that “limits” the evolutionary potential of living things, like bacteria, in their ability to evolve some functions but not others?

I propose that the answer can be found in the number and density of beneficial “steppingstones” available (in the form of genetic sequences). For forms of antibiotic resistance that are gained by blocking the antibiotic-target function, there are lots of beneficial steppingstones very close together, but not so for the enzymatic functions of lactase, nylonase or penicillinase. Relatively speaking, there are very few such enzymes, compared to the total number of possible sequences. 

For example, there are 676 potential two-letter words in the English language. Of these, 96 are defined as meaningful, creating a ratio of meaningful to meaning- less of 1 in 7. Now, there are 296 more meaningful three-letter words, totaling 972, but the total number of potential words increases 26 fold to 17,576. Since the number of meaningful words only increased by a fraction of this amount, the ratio of meaningful to meaningless dropped to 1 in 18. 

  Still, such ratios are relatively high, and random walk can get from any one-, two-, or three-letter words to any other via a path of meaningful words, as in the steppingstone sequence of cat – hat – bat – bad – bid – did – dig – dog. “Evolution” (changing meaning or “function”) at this level is rather simple because the stepping-stones are so close together. But, with each additional minimum letter requirement, the growth of the meaningless sequences quickly outpaces the growth of the total number of meaningful sequences, and the ratio of meaningful to meaningless gets smaller and smaller at an exponential rate. 

For example, there are around 30,000 meaningful seven-letter words and combinations of smaller words totaling seven letters, but there are 8,031,810,176 potential seven-letter sequences. This produces a situation in which an average meaningful seven-letter sequence is surrounded by over 250,000 meaningless sequences. Obviously then, compared to three-letter steppingstones, it is much harder to “evolve” between meaningful seven-letter steppingstones without having to cross through a little ocean of meaningless sequences. 

The same thing happens with the genetic codes in living things. The more genetic letters that are required to achieve a particular function, and the higher the level of the specificity of their arrangement, the more junk there is compared to the relatively few beneficial sequences at such a level of complexity.

For example, a simple BLAST ¹⁴ database search of known proteins will show that the shortest working lactase enzyme found in a living organism seems to require around 400 amino acids at minimum with at least a fair degree of specificity. Some estimates suggest that the total number of beneficial sequences at the 400-amino-acid level of specified complexity totals less than 10¹⁰⁰ sequences.^15,16 Now, considering that the total number of atoms in the entire known universe is around 10⁸⁰, this 10¹⁰⁰ number seems absolutely huge! ¹⁷ Huge, that is, until one considers that there are over 10⁵²⁰ possible sequences at this level of complexity, which creates a ratio of beneficial to non-beneficial sequences of about 1 in 10⁴⁰⁰ (which is like finding a single atom in zillions of universes).  The actually ratio of lactases vs. non-lactases is probably quite a bit lower than that due to a wider range of sequence flexibility (i.e., lower specificity). 

Nylonase, on the other hand, is in exactly the same boat.  The nylonase enzyme originally evolved via a frame shift mutation in a stretch of DNA coding for a 472aa protein.  The frame shift mutation was caused by the insertion of a single thymine nucleotide at just the right spot to create a "start codon" and produce an entirely new protein sequence of 392aa (6-aminohexanoic acid linear oligomer hydrolase).²⁰ Other nylonase proteins have been coded for by as few as 355aa with what seems to be fairly loose minimum sequence specificity - even compared to the lactase enzymatic function.²¹   Statistically, this means a nylonase enzyme is at least as easy to evolve as a lactase enzyme if not easier.   

To further illustrate the concept of an expanding sequence space and potential evolutionary steppingstones within that space, consider Choi and Kim's paper (illustrated figures above and to the right) and their "global view of the protein structure space."  Choi and Kim did something very interesting. They mapped "1,898 nonredundant protein structures from Protein Data Bank [onto] 3D space [down from the hyperdimensional space of protein-sequence/structure space] to visualize the major feature of the map. The protein structure space is sparsely populated, and all of the proteins of known structures cluster mostly into four elongated regions, which correspond approximately to four SCOP classes (all-, all-, +, and /) of protein structures indicated by red, yellow, purple, and cyan spheres, respectively. The small proteins and multidomain protein classes are represented by green and black spheres, respectively. All structural class assignments were based on the SCOP classification. Three axes are drawn in to visualize high-population regions of all-, all-, and / class proteins, and the "origin" is represented by a large orange ball at the point where two of the axes meet." ¹⁸

Given this description, notice how the small proteins (green spheres) are much more closely spaced and clustered together compared to the multidomain proteins (black spheres) and other larger proteins (other colors) which occupy much much larger sequence and structural spaces. There is a progressive increase in the average distance between "viable" spheres with increasing size requirements. Again, this only highlights the fact that increasing structural threshold requirements produce a lower ratio and wider non-beneficial gaps between potentially viable and beneficial protein-based systems in sequence/structure space. There is a progressive increase in the average distance between beneficial protein structures with increasing size requirements. This feature is illustrated in an even clearer way in the figure above (c).  In this figure you will note a size scale where the shortest proteins are colored dark blue, medium sized proteins green to yellow, and the largest proteins red.  Guess which beneficial protein systems have the greatest average distance from each other? 

Also, consider that the three dimensional illustration presented is a dramatic under characterization of the actual distance that exists in hyperdimensional sequence/structure space.  It is like projecting the shadows of widely-spaced objects that exist in three dimensional space onto a two dimensional screen.  The resulting dots on the two-dimensional screen would appear much closer together than they really are in three dimensional space.  Now, extrapolate this effect by hundreds and thousands of dimensions (one extra dimension for every one amino acid residue increase in protein system size) to understand the true gap distances illustrated by Choi and Kim.

Erich Bornberg-Bauer's paper dealing with model protein structures (comparable to real proteins) supports the notion that sequence space is sparsely populated with fairly evenly distributed viable proteins even at low-levels of structural threshold requirements - features which I propose only become exponentially more and more accentuated with each step up the ladder of minimum structural threshold requirements.

"Roughly speaking, however, distances are randomly distributed. This means that, although only a small fraction of sequence space yields uniquely folding sequences, sequence space is occupied nearly uniformly. No "higher order" clustering (i.e., except the trivial case of the homologous sequences) is visible." ¹⁹

Real Life

Of course, since nature cannot tell the difference between two meaningless genetic sequences, it cannot select between them, making natural selection blind to such neutral changes. Since there are no recognizable “steppingstones” close by, all that nature has left, to find new beneficial sequences, is a blind random walk through enormous piles of junk sequences. Of course, this random, curvy walk takes a lot longer than a direct walk would take, and the time involved increases  exponentially with each increase in the minimum sequence and specificity requirements for a particular function. Random selection of sequences within sequence space starting from a beneficial island (like throwing darts at a dartboard) has no statistical advantage when it comes to finding novel beneficial sequences over neutral random walk.  This prediction is reflected in real life by an exponential decline in the ability of mindless evolutionary processes to evolve anything beyond the lowest levels of functional complexity.

Many simple functions, such as de novo antibiotic resistance, are easy to evolve for any bacterial colony in short order. Moving up a level of complexity, there are far fewer examples of single protein enzymes evolving where a few hundred amino acids at minimum are required to work together at the same time (and many types of bacteria cannot evolve even at this level). However, there are absolutely no examples in the scientific literature of any function requiring more than a thousand or so amino acids working at the same time (as in the simplest bacterial motility system) ever evolving — period. The beneficial “steppingstones” are just too far apart due to all the junk that separates the few beneficial islands of function from every other island in the vast universe of junk sequences at such levels of informational complexity. The average time needed to randomly sort through enough junk sequences to find any other beneficial function at such a level of complexity quickly works its way into trillions upon trillions of years — even for an enormous population of bacteria (all the bacteria on Earth: ~1e30) with a high mutation rate (one mutation per 100,000 base pairs per individual every 20 minutes).  (Link)

At this point the mindless processes of evolution simply become untenable as any sort of viable explanation for the high levels of diverse complexity that we see within all living things. The only process left that is known to give rise to functional systems at comparable levels of complexity involves human intelligence or beyond. No lesser intelligence, and certainly no other known mindless processes, have ever come close to producing something like the informational complexity found in the simplest bacterial motility system. (Link)

References:

1. Miller, Kenneth R., Finding Darwin’s God, HarperCollins Publishers, 1999.

2. Behe, Michael J. Darwin’s Black Box, The Free Press, 1996. 

3. Anand Sukhan, Tomoko Kubori, James Wilson, and Jorge E. Galán. 2001. Genetic Analysis of Assembly of the Salmonella enterica Serovar Typhimurium Type III Secretion-Associated Needle Complex. J. Bacteriology 183: 1159-1167.  

4. Macnab, R. M., 1999. The bacterial flagellum: reversible rotary propellor and type III export apparatus. J Bacteriology. 181 (23), 7149-7153.

5. He, S. Y., 1998. Type III protein secretion in plant and animal pathogenic bacteria. Annual Reviews in Phytopathology. 36, 363-392.  

6. Kim, J. F., 2001. Revisiting the chlamydial type III protein secretion system: clues to the origin of type III protein secretion. Trends Genet. 17 (2), 65-69.  

7. Plano, G. V., Day, J. B. and Ferracci, F., 2001. Type III export: new uses for an old pathway. Mol Microbiol. 40 (2), 284-293.  

8. Nguyen, L., Paulsen, I. T., Tchieu, J., Hueck, C. J. and Saier, M. H., Jr., 2000. Phylogenetic analyses of the constituents of Type III protein secretion systems. J Mol Microbiol Biotechnol. 2 (2), 125-144.  

9. Johnson GR, Jain RK, Spain JC. "Origins of the 2,4-dinitrotoluene pathway." J Bacteriol. 2002 Aug;184(15):4219-32. (Free full-text article Link)

10. Emiko Matsuzaka, Nobuhiko Nomura, Hideaki Maseda, Hiroshi Otagaki, Toshiaki Nakajima-Kambe, Tadaatsu Nakahara and Hiroo Uchiyama Participation of Nitrite Reductase in Conversion of NO₂^- to NO₃ ^- in a Heterotrophic Nitrifier, Burkholderia cepacia NH-17, with Denitrification Activity, Microbes and Environments, Vol. 18 (2003) , No. 4 pp.203-209 (Link)

11. Talk Origins Debate, February 16, 2007 (Link)

12. B.G. Hall, Evolution on a Petri Dish.  The Evolved B-Galactosidase System as a Model for Studying Acquisitive Evolution in the Laboratory, Evolutionary Biology, 15(1982): 85-150.

13. Behe, Michael J., "A True Acid Test" - Response to Kenneth Miller, Discovery Institute, May 2002. (Link)

14. BLAST Search: http://www.ncbi.nlm.nih.gov/BLAST

15. Yockey, H.P. 1992. Information Theory and Molecular Biology. Cambridge University Press, pp. 255, 257.  

16. Yockey, H.P., On the information content of cytochrome C, Journal of Theoretical Biology , 67 (1977), p. 345-376.  

17. Anonymous. n.d. The Universe. National Solar Observatory, Sacramento Peak. http://www.nso.edu/sunspot/pr/answerbook/universe.html/  [ Ed. note: The number of atoms according to this reference is estimated to be 10 ⁷⁹ .]

18. In-Geol Choi^*, and Sung-Hou Kim, Evolution of protein structural classes and protein sequence families, PNAS | September 19, 2006 | vol. 103 | no. 38 | 14056-14061 ( Link )

19. Erich Bornberg-Bauer, How Are Model Protein Structures Distributed in Sequence Space? Biophysical Journal, Volume 73, November 1997, 2393-2403 ( Link )

20. Susumu Ohno, "Birth of a unique enzyme from an alternative reading frame of the pre-existed, internally repetitious coding sequence",  Proc. Natl. Acad. Sci. USA, Vol. 81, pp. 2421-2425, April 1984. ( Link )  See also: New Mexicans for Science and Reason

21. Seiji Negoro, Shinji Kakudo, Itaru Urabe, and Hirosuke Okadam, "A New Nylon Oligomer Degradation Gene (nylC) on Plasmid pOAD2 from a Flavobacterium sp.," Journal of Bacteriology, Dec. 1992, p. 7948-7953. ( Link )

See Also:  Miller's Lecture at Case Western University: YouTube Link

Addendum:

 

The metabolic characteristics of the NO₂ ^- transforming activities of Burkholderia cepacia NH-17, which was isolated as a heterotrophic nitrifying bacterium with O₂ tolerant denitrification activity, were characterized. The conversion of NO₂^- to N₂O and NO₃^- occurred concomitantly with a decrease in NO₂^- under aerobic conditions in growing cultures. In an in vivo assay, production of N₂O and NO₃^- was induced by NO₂^- as an inducer for denitrification, and nitrite reductase activity in sonicated fraction (NiR) assay indicated that in vitro nitrite reductase activity was also induced by NO₂^-. These results suggested that nitrification and denitrification in Burkholderia cepacia NH-17 might be closely related. Therefore, we constructed a nirS knockout mutant of Burkholderia cepacia NH-17. The mutant had no in vitro nitrite reductase activity and did not convert NO₂ ^- to N₂O and NO₃^-. These properties were restored by introducing the intact nirS gene into the mutant strain, indicating that reduction of NO₂ ^- to NO is necessary for the conversion of NO₂ ^- to NO₃^- in Burkholderia cepacia NH-17.¹⁰

 

 

 

 

Review of Miller's interview with NOVA (Link):

My comments are indented and are in Blue:

 

In Defense of Evolution

Dr. Kenneth Miller is as familiar as anyone in the scientific community with the intelligent-design movement and its attempts to undermine the theory of evolution. A professor of biology at Brown University and coauthor (with Joe Levine) of the standard high-school textbook Biology, Miller testified at the Dover trial as an expert witness for the plaintiffs, the Dover parents who brought suit against their town's school board. Here, Miller, who stresses that he is also a man of faith, talks about why evolution matters, what flaws he sees in the intelligent-design argument, and why the Dover decision hardly means the end of the controversy.

Faith and reason

Q: Why is evolution so controversial?

Kenneth Miller: I think one of the reasons why evolution is such a contentious issue, quite frankly, is the same reason you can go into a bar and start a fight by saying something about somebody's mother. Evolution concerns who we are and how we got here. And to an awful lot of people, the story of evolution, the story of our continuity with every other living thing on this planet, that's not a story they want to hear.

They favor an entirely different story, in which our ancestry is separate, our biology distinct, and the whole notion of our lineage traceable not to other organisms, but to some sort of divine power and divine presence. But it's absolutely true that our ancestry traces itself along the same thread as that of every other living organism. That, for many people, is the unwelcome message, and I think that's why evolution has been, is, and will remain such a controversial idea for many years to come.

Sean Pitman: I agree.  All ideas that affect one's view of where one came from and why one is here on this planet are bound to be tied up with a fair degree of emotion - at least for most people.  What is interesting is that scientists are not immune from this sort of emotional bias. Evolutionists, just like creationists and those who believe in some form of intelligent design or input into the origins of life, are often quite passionate about their respective positions on origins.  Scientists are no more immune from this sort of bias than are philosophers, plumbers, or preachers.

Q: Where do you come from personally on this topic?

Miller: I think that faith and reason are both gifts from God. And if God is real, then faith and reason should complement each other rather than be in conflict. Science is the child of reason. Reason has given us the ability to establish the scientific method to investigate the world around us, and to show that the world and the universe in which we live are far vaster and far more complex, and I think far more wonderful, than anyone could have imagined 1,000 or 2,000 years ago.

Does that mean that scientific reason, by taking some of the mystery out of nature, has taken away faith? I don't think so. I think by revealing a world that is infinitely more complex and infinitely more varied and creative than we had ever believed before, in a way it deepens our faith and our appreciation for the author of that nature, the author of that physical universe. And to people of faith, that author is God.

Now, I'm a scientist and I have faith in God. But that doesn't make faith a scientific proposition. Faith and reason are both necessary to the religious person for a proper understanding of the world in which we live, and there is ultimately no necessary contradiction between reason and faith.

"Whether God exists or not is not a scientific question."

Sean Pitman: I'm most intrigued by Miller's thoughts here.  How is Miller's description of "faith" in God any better than wishful thinking or a child's belief in Santa Claus?  I may be wrong, but it seems to me that Miller is talking about some sort of fantasy or concept of completely blind "faith" where one believes in this or that hopeful reality based on absolutely nothing but feelings or desire. In my opinion, those like Richard Dawkins are correct in becoming quite exasperated by such thinking and rightfully calling it "The God Delusion".  

While I personally do believe an intelligent Creator God, I do so because I think there is solid, testable, falsifiable evidence for a God-like higher power that goes far beyond human-level intelligence, power, and creativity.  If I did not at least think I recognized such evidence, there is no way I would actually worship a God for which I saw no physical evidence of his/her/its existence or interaction with any aspect of nature.

Q: What's wrong with bringing God into the picture as an explanation?

Miller: Supernatural causes for natural phenomena are always possible. What's different, however, in the scientific view is the acknowledgement that if supernatural causes are there, they are above our capacity to analyze and interpret.

Saying that something has a supernatural cause is always possible, but saying that the supernatural can be investigated by science, which always has to work with natural tools and mechanisms, is simply incorrect. So by placing the supernatural as a cause in science, you effectively have what you might call a science-stopper. If you attribute an event to the supernatural, you can by definition investigate it no further.

If you close off investigation, you don't look for natural causes. If we had done that 100 years ago in biology, think of what we wouldn't have discovered because we would have said, "Well, the designer did it. End of story. Let's go do something else." It would have been a terrible day for science.

Sean Pitman: I see this argument all the time and am always amazed by how many otherwise intelligent men and women use it and/or are taken in by it.  If a God or someone with at least high-level or God-like powers and/or intelligence decided to manipulate nature in any way, Miller and many other scientists actually argue that it would be impossible for humans to recognize any kind of manipulation of nature as being the result of deliberate intent or "artifact".  Yet, when it comes to the detection of deliberate human activity, activity that is arguably far less intelligent than what anyone would call "God-like", scientists don't seem to have any problem detecting design. 

Entire scientific disciplines are built up around the concept of detecting deliberate activity behind various phenomena in nature - - to include forensic science and anthropology.  Of course, these disciplines are built around previous experience with and direct observations of humans in action. Yet, there are scientists who do in fact propose that highly intelligent activity, even superhuman-level intelligence, can be detected without any need for knowledge concerning the actual identity, motive, or method of the intelligent agents.  These scientist spend their time searching for signs of intelligence coming from outer space - -  as in the search for extraterrestrial intelligence or SETI.

The argument is, of course, that humans and alien intelligences living somewhere in outer space are "natural", not "supernatural", and can therefore be potentially detected by scientific investigation. So, what if someone with God-like intelligence decided to act in a similar way to manipulate nature in a way that would at least simulate what human or alien intelligences could or would do that would be detectable as artifact?  Would it then be possible to detect such activity as at least intelligent or artifactual in nature? - - Rather than the result of some as yet unknown non-intelligent natural process? 

Q: Does science have limits to what it can tell us?

Miller: If science is competent at anything, it's in investigating the natural and material world around us. What science isn't very good at is answering questions that also matter to us in a big way, such as the meaning, value, and purpose of things. Science is silent on those issues. There are a whole host of philosophical and moral questions that are important to us as human beings for which we have to make up our minds using a method outside of science.

Sean Pitman: It just so happens that I like vanilla ice cream.  That's a fact.  And, it didn't take any scientific investigation for me to discover this fact.  It is not subject to testing or falsification by me or anyone else.  It just is.  It is an internally derived truth.  Is it important to me? Well, I'm kind of glad I know it as a truth.  It saves me a lot of time and frustration when I go to pick out an ice cream to buy at the store.

Is a belief in the existence of God as a "truth" kind of like the truth that I like vanilla ice cream?  Well, I may really like the concept or idea of a God or God-like being.  It may really appeal to me.  However, once I start suggesting how this God would act or actually did act or interact with the physical world that exists outside of my own mind, I have moved into the realm of science.  Making suggestions or assertions about what God does or did outside of my own mind without at least some physical evidence to back up such assertions is like taking on a form of schizophrenia or deliberate mental delusions that are based on nothing more than mental projections or very strong mental or emotional desires - - which do not necessarily have anything to do with the reality that actually exists outside and independent of ones own mind.

Q: Can science prove or disprove the existence of a creator, of God?

Miller: Whether God exists or not is not a scientific question.

Sean Pitman: Actually, it is, or it at least could be a scientific question.  It all depends on if God wishes to act in a way that is detectable as "artifactual" from a human perspective.  If a God does actually exists that wishes or has actually acted in such a way, such actions could, theoretically at least, be detectable as "deliberate" and "intelligent" - - just as any alien intelligence could be detectable as such by SETI scientists.

Evolution in a nutshell

Q: What is evolution exactly?

Miller: Well, everyone knows that evolution, in a sense, is change over time.

Sean Pitman: Well, lots of things change over time.  Even intelligent design advocates and creationists recognize this fact.  The question is: How do living things change over time . . . and to what degree?  For example, there is a distinct difference between the changes proposed by Gregor Mendel over time vs. those suggested by Darwin .  Darwinian-style change cannot be explained using Mendelian-style change alone.  Therefore, the changes over time proposed by Darwin require a different sort of mechanism that goes beyond the mechanism of Mendelian-type change. 

But what few people understand is how straightforward the nature of this change is. It's important to understand, first of all, that individuals don't evolve. I'm not evolving into something else, and my dog isn't evolving into something else. I'm going to remain a human being, he's going to remain a dog. That's the way things are going to work. What changes over time are populations of individuals, for very straightforward reasons.

Sean Pitman: Strictly speaking, individuals do "change" over time.  Parts of individuals even undergo what could be called Darwinian-style evolution over time - such as the human immune system which is often used as an example of functional evolution in action.  Some individuals evolve entirely new proteins or chimeric protein combinations, such as the famous BCL/ABL tyrosine kinase protein seen in people who develop or evolve chronic myelogenous leukemia (CML).  However, it is true that such "changes" aren't going to change a dog into a chicken, etc. 

Number one, every species shows variation among individual members of that population.

Sean Pitman: This is true.

Number two, individuals in a population show what biologists call differential reproductive success. Some individuals leave more offspring than others. Some people have no children; some people have big families.

Sean Pitman: Also true.

Finally, one of the factors that influences differential reproductive success is how well-suited individuals are to the present environment in which they find themselves—how good they are at obtaining food, defending themselves against their enemies, resisting disease, and finding and meeting a member of the opposite sex and raising offspring. All these things matter.

Sean Pitman: Right . . .

What Darwin appreciated is that nature herself selects from variants in the population for those that are best able to succeed in this race for differential reproductive success. Over time, and given a steady input of new variation into the population, that can change the average characteristics of a species, and it can split one species into two.

Sean Pitman: Absolutely.  A good example would be horses and donkeys - - two "species" that clearly had a common ancestor, share the same basic "gene pool" and can interbreed to produce viable if not virile offspring (i.e., mules and/or hinnies). However, Mendelian variation can also change the average characteristics of a population over time via the guidance of natural selection.  Yet, Mendelian variation cannot create truly novel gene pools with unique functional elements present in the offspring which were not already present in the parent population.

Those species, those two groups, can then go on changing in different directions. That's what leads to the formation of yet more new species. Nature herself automatically selects for favorable variations, and this is the driving engine of evolutionary change. That, in a nutshell, is what evolution is.

Sean Pitman:  This definition of evolution allows for more types of "change" that just Darwinian-style change over time.  The real issue here is over the concept of Darwinian-style evolution where truly novel functional elements are added to gene pools over time.  That is the definition of Darwinian-style evolution, in a nutshell. 

The question then is: Can Darwinian-style evolution happen, and if so, does it have any evident limitations when it comes to the type or nature or degree of novel functional elements that can be produced? 

Evolutionists strongly believe that given enough time and the appropriate environments or environmental changes or variations, the answer to this question is no - - There is no significant limit to the nature or degree of novel functional systems that can be added to any gene pool.

It is this notion that creationists and intelligent design theorists wish to challenge.  Many, even a number of very well educated scientists, to include several Nobel Laureates, are starting to question this particular claim of mainstream evolutionary theory.

Q: Why is evolution important? How does it affect people in their everyday lives?

Miller: We should care about evolution because it concerns who we are, where we came from, why we are the way we are, and maybe even where we're going.

Sean Pitman:  That's true . . .

The whole notion that biology is wrapped up in the idea of evolution is extremely important to experimental biologists, because otherwise, to paraphrase another scientist, biology is nothing but stamp collecting. It's an exercise in which you say, "Here's a worm and here's how worms work, and here's this type of cell and here's how this cell works. And here is a plant, and here is how plants work."

If they're all completely unrelated, then biology is not a unified science.

Sean Pitman