April 13, 2004 | David F. Coppedge

Fake Darwinism Created by Intelligent Design

Scientists have created enzymes with enhanced ability to select between left- and right-handed molecules, using an “evolutionary” process, claims Manfred Reetz in a Perspective article in PNAS:1

A fundamentally new approach to asymmetric catalysis in organic chemistry is described based on the in vitro evolution of enantioselective enzymes.  It comprises the appropriate combination of gene mutagenesis and expression coupled with an efficient high-throughput screening system for evaluating enantioselectivity (enantiomeric excess assay).  Several such cycles lead to a “Darwinistic” process, which is independent of any knowledge concerning the structure or the mechanism of the enzyme being evolved.  The challenge is to choose the optimal mutagenesis methods to navigate efficiently in protein sequence space.  As a first example, the combination of error-prone mutagenesis, saturation mutagenesis, and DNA-shuffling led to a dramatic enhancement of enantioselectivity of a lipase acting as a catalyst in the kinetic resolution of a chiral ester.  Mutations at positions remote from the catalytically active center were identified, a surprising finding, which was explained on the basis of a novel relay mechanism.  The scope and limitations of the method are discussed, including the prospect of directed evolution of stereoselective hybrid catalysts composed of robust protein hosts in which transition metal centers have been implanted.

Basically, researchers built enzymes top-down instead of bottom-up.  Instead of the old “rational design” method, trying to construct an active site to perform the function needed, they started with the function they wanted, and iteratively selected any “mutants” that came closest to doing the job, without stipulating how they did it.  The “surprising finding” he spoke of was that a distant mutation, far from the active site, actually improved the performance of the enzyme.

1Manfred T. Reetz, “Controlling the enantioselectivity of enzymes by directed evolution: Practical and theoretical ramifications,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0306866101, published online before print April 12, 2004.

He put “Darwinistic” in quotes, because it was not really Darwinistic, it was Designistic.  The scientists played the role of designer by carefully selecting the results and directing the outcome.  This paper, like others before it, gives two false impressions: (1) that Darwinism achieved the high specificity of proteins in the past, and (2) that Darwinian theory is a boon to science in the present.  This is nothing but name-dropping.  Charlie had nothing to do with it.
    If this were Darwinism, there would be no “directed evolution” (an oxymoron), because there would be no direction.  Here, the scientists had a goal: they wanted enantioselective enzymes.  Their “mutation and selection” process was results-driven by artificial selection, a form of intelligent design.  Yet Reetz illogically claims, without any evidence or support (only belief), “Enzymes are products of evolution, and might therefore be expected to function with high enantioselectivity only with natural substrates under physiological conditions.”  Then, in the very next breath, he falsifies this evolutionary prediction: “However, it is well known that this is not the case, because a surprisingly large number of unnatural compounds are converted with high enantioselectivity, even in organic solvents.”  So does this convert him to ID theory?  No, he just waltzes into the problem at hand: “Nevertheless, the problem of substrate specificity persists.  In such cases several approaches to enhance enzyme stereoselectivity have been described, including site-specific mutagenesis based on theoretical considerations…” la te da, blah blah, and so on, and so forth, so we’ll design an enzyme with a creative method and give Charlie the glory.
    The difference between this method and the traditional bottom-up approach Reetz calls “rational design” can be compared to the difference between engineering and management.  The engineer knows the physical laws and properties of the widget he is designing, and organizes the parts specifically toward the solution.  The manager just says, “Build me a widget that flies.”  An upper manager might devise a contest between engineers to see who can come up with the best design.  All the manager cares about is the results: will it fly?  He weeds out the losers and rewards the winners.  The winner gets more resources to refine the design until an optimal design is produced.  Even if the engineer uses trial and error and chance, given enough trials a working prototype will emerge as long as intelligence is directing the process toward a goal.  In a similar way, these researchers did not need to know all the details of the structure of the enzyme they wanted to create; they just mutated ingredients and selected the few that worked, then iterated the process until the best design was filtered out of the pile.  They managed the process rather than engineering it.  Only Dilbert would nominate his manager for a Darwin award.
    Another thing.  The “surprising” discovery Reetz made also argues against Darwinism.  His team found that a remote amino acid, far from the active site, was essential to the function.  He was so surprised by this he called it a paradigm-shifting finding: “This observation leads to a change in paradigm, because all previous attempts to influence enantioselectivity of an enzyme by using site-specific mutagenesis had focused on amino acid substitutions near the active center.  Such protein engineering was designed to “carve” an appropriate chiral pocket at the active center, in line with Fischer’s “lock-and-key” hypothesis or modified versions such as Koshland’s induced fit.  Later, he adds, “… our studies show that the long-standing dogma regarding the necessity of amino acid substitutions exclusively at the active site to influence enantioselectivity no longer holds.”  What this means is that an enzyme is designed all the way through, not just at the active site.  The “lock and key” fit of an enzyme to its substrate is amazing enough, but to think that distant amino acids actually affect the workings of the molecular machine calls into question the belief that proteins can be mutated at will, as long as they are far from the active site.  This underscores the improbability of getting all the amino acids in the right order, as described in our online book, Evolution: Possible or Impossible?
    Let’s give credit where credit is due.  This experiment is all about design.  Calling this “Darwinistic” is like calling Boeing a manufacturer of tornados in junkyards.

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Categories: Intelligent Design

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