Molecular Machines that Defy Darwin

When Dogma Does Not Explain Reality, What Is a True Believer to Do?

Long before the advent of modern technology, students of biology compared the workings of life to machines. In re­cent decades, this comparison has become stronger than ever. As a paper in Nature Reviews Molecular Cell Biology states, “Today biology is revealing the importance of ‘molecular machines’ and of other highly organized molecular structures that carry out the complex physico-chemical processes on which life is based.” Likewise, a paper in Nature Methods observed that “[m]ost cellular functions are executed by protein complexes, acting like molecular ma­chines.”

A molecular machine, according to an article in the journal Accounts of Chemical Research, is “an assemblage of parts that transmit forces, motion, or energy from one to another in a predetermined manner.” A 2004 article in An­nual Review of Biomedical Engineering asserted that “these machines are generally more efficient than their macro-scale counterparts,” further noting that “[c]ountless such machines exist in nature.” Indeed, a single research project in 2006 reported the discovery of over 250 new molecular machines in yeast alone!

Molecular machines have posed a stark challenge to those who seek to understand them in Darwinian terms as the products of an undirected process. In his 1996 book Darwin’s Black Box: The Biochemical Challenge to Evolu­tion, biochemist Michael Behe explained the surprising discovery that life is based upon machines:

“Shortly after 1950 science advanced to the point where it could determine the shapes and properties of a few of the molecules that make up living organisms. Slowly, painstakingly, the structures of more and more biological molecules were elucidated, and the way they work inferred from countless experiments. The cumulative results show with piercing clarity that life is based on machines—machines made of molecules! Molecular machines haul cargo from one place in the cell to another along “highways” made of other molecules, while still others act as cables, ropes, and pulleys to hold the cell in shape. Machines turn cellular switches on and off, sometimes killing the cell or causing it to grow. Solar-powered machines capture the energy of photons and store it in chemicals. Electrical ma­chines allow current to flow through nerves. Manufacturing machines build other molecular machines, as well as themselves. Cells swim using machines, copy themselves with machinery, ingest food with machinery. In short, high­ly sophisticated molecular machines control every cellular process. Thus, the details of life are finely calibrated and the machinery of life enormously complex.”

Behe then posed the question, “Can all of life be fit into Darwin’s theory of evolution?” and answered: “The com­plexity of life’s foundation has paralyzed science’s attempt to account for it; molecular machines raise an as-yet im­penetrable barrier to Darwinism’s universal reach.”

Even those who disagree with Behe’s answer to that question have marveled at the complexity of molecular ma­chines. In 1998, former president of the U.S. National Academy of Sciences Bruce Alberts wrote the introductory arti­cle to an issue of Cell, one of the world’s top biology journals, celebrating molecular machines. Alberts praised the “speed,” “elegance,” “sophistication,” and “highly organized activity” of “remarkable” and “marvelous” structures in­side the cell. He went on to explain what inspired such words:

The entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines. . . . Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts.

Likewise, in 2000 Marco Piccolini wrote in Nature Reviews Molecular Cell Biology that “extraordinary biological machines realize the dream of the seventeenth century scientists… that ‘machines will be eventually found not only unknown to us but also unimaginable by our mind.’ ” He notes that modern biological machines “surpass the expec­tations of the early life scientists.”

A few years later, a review article in the journal Biological Chemistry demonstrated the difficulty evolutionary sci­entists have faced when trying to understand molecular machines. Essentially, they must deny their scientific intui­tions when trying to grapple with the complexity of the fact that biological structures appear engineered to the sche­matics of blueprints:

Molecular machines, although it may often seem so, are not made with a blueprint at hand. Yet, biochemists and molecular biologists (and many scientists of other disciplines) are used to thinking as an engineer, more precisely a reverse engineer. But there are no blueprints … ‘Nothing in biology makes sense except in the light of evolution’: we know that Dobzhansky (1973) must be right. But our mind, despite being a product of tinkering itself strangely wants us to think like engineers.

But do molecular machines make sense in the light of undirected Darwinian evolution? Does it make sense to deny the fact that machines show all signs that they were designed? Michael Behe argues that in fact molecular ma­chines meet the very test that Darwin posed to falsify his theory, and indicate intelligent design.

Darwin knew his theory of gradual evolution by natural selection carried a heavy burden:

“If it could be demonstrated that any complex organ existed which could not possibly have been formed by numer­ous, successive, slight modifications, my theory would absolutely break down.

“… What type of biological system could not be formed by ‘numerous successive slight modifications’? Well, for starters, a system that is irreducibly complex. By irreducibly complex I mean a single system which is composed of several interacting parts that contribute to the basic function, and where the removal of any one of the parts causes the system to effectively cease functioning.”

Molecular machines are highly complex, and in many cases we are just beginning to understand their inner work­ings. As a result, while we know that many complex molecular machines exist, to date only a few have been studied sufficiently by biologists so that they have been directly tested for irreducible complexity through genetic knockout experiments or mutational sensitivity tests. What follows is a non-exhaustive list briefly describing 20 molecular ma­chines identified in the scientific literature. The first section will cover molecular machines that scientists have argued show irreducible complexity. The second section will discuss molecular machines that may be irreducibly complex but have not been studied in enough detail yet by biochemists to make a conclusive argument.

Selected List of Molecular Machines:

Molecular Machines that Scientists Have Argued Show Irreducible Complexity

1. Bacterial Flagellum The flagellum is a rotary motor in bacteria that drives a propeller to spin, much like an outboard motor, powered by ion flow to drive rotary motion. Capable of spinning up to 100,000 rpm, one paper in Trends in Microbiology called the flagellum “an exquisitely engineered chemiosmotic nanomachine; nature’s most powerful rotary motor, harnessing a transmembrane ion-motive force to drive a filamentous propeller.” Due to its motor-like structure and internal parts, one molecular biologist wrote in the journal Cell, “[m]ore so than other mo­tors, the flagellum resembles a machine designed by a human.” Genetic knockout experiments have shown that the E. coli flagellum is irreducibly complex with respect to its approximately 35 genes. Despite the fact that this is one of the best studied molecular machines, a 2006 review article in Nature Reviews Microbiology admitted that “the flagel­lar research community has scarcely begun to consider how these systems have evolved.”

  1. Eukaryotic Cilium The cilium is a hair-like, or whip-like, structure that is built upon a system of microtubules, typically with nine outer microtubule pairs and two inner microtubules. The microtubules are connected with nexin arms, and a paddling-like motion is instigated with dynein motors. These machines perform many functions in Eu­karyotes, such as allowing sperm to swim or removing foreign particles from the throat. Michael Behe observes that the “paddling” function of the cilium will fail if it is missing any microtubules, connecting arms, or lacks sufficient dynein motors, making it irreducibly complex.
  2. Aminoacyl-tRNA Synthetases (aaRS) aaRS enzymes are responsible for charging tRNAs with the proper amino acid so they can accurately participate in the process of translation. In this function, aaRSs are an “aminoacylation machine.” Most cells require twenty different aaRS enzymes, one for each amino acid, without which the transcrip­tion/translation machinery could not function properly. As one article in Cell Biology International stated: “The nu­cleotide sequence is also meaningless without a conceptual translative scheme and physical ‘hardware’ capabilities. Ribosomes, tRNAs, aminoacyl tRNA synthetases, and amino acids are all hardware components of the Shannon mes­sage ‘receiver’. But the instructions for this machinery is itself coded in DNA and executed by protein ‘workers’ pro­duced by that machinery. Without the machinery and protein workers, the message cannot be received and under­stood. And without genetic instruction, the machinery cannot be assembled.” Arguably, these components form an irreducibly complex system.
  3. Blood Clotting Cascade The blood coagulation system “is a typical example of a molecular machine, where the assembly of substrates, enzymes, protein cofactors and calcium ions on a phospholipid surface markedly accelerates the rate of coagulation.” According to a paper in BioEssays, “the molecules interact with cell surface (molecules) and other proteins to assemble reaction complexes that can act as a molecular machine.” Michael Behe argues, based upon experimental data, that the blood clotting cascade has an irreducible core with respect to its components after its initiation pathways converge.
  4. Ribosome The ribosome is an “RNA machine” that “involves more than 300 proteins and RNAs” to form a com­plex where messenger RNA is translated into protein, thereby playing a crucial role in protein synthesis in the cell. Craig Venter, a leader in genomics and the Human Genome Project, has called the ribosome “an incredibly beautiful complex entity” which requires a “minimum for the ribosome about 53 proteins and 3 polynucleotides,” leading some evolutionist biologists to fear that it may be irreducibly complex.
  5. Antibodies and the Adaptive Immune System Antibodies are “the ‘fingers’ of the blind immune system—they allow it to distinguish a foreign invader from the body itself.” But the processes that generate antibodies require a suite of molecular machines. Lymphocyte cells in the blood produce antibodies by mixing and matching portions of special genes to produce over 100,000,000 varieties of antibodies. This “adaptive immune system” allows the body to tag and destroy most invaders. Michael Behe argues that this system is irreducibly complex because many compo­nents must be present for it to function: “A large repertoire of antibodies won’t do much good if there is no system to kill invaders. A system to kill invaders won’t do much good if there’s no way to identify them. At each step we are stopped not only by local system problems, but also by requirements of the integrated system.”

Additional Molecular Machines

May be irreducibly complex but have not been studied in enough detail yet to make a conclusive argument.

  1. Spliceosome The spliceosome removes introns from RNA transcripts prior to translation. According to a paper in Cell, “In order to provide both accuracy to the recognition of reactive splice sites in the pre-mRNA and flexibility to the choice of splice sites during alternative splicing, the spliceosome exhibits exceptional compositional and structu­ral dynamics that are exploited during substrate-dependent complex assembly, catalytic activation, and active site re­modeling.” A 2009 paper in PNAS observed that “[t]he spliceosome is a massive assembly of 5 RNAs and many pro-teins”—another paper suggests “300 distinct proteins and five RNAs, making it among the most complex macromolecular machines known.”
  2. F0F1 ATP Synthase According to cell biologist and molecular machine modeler David Goodsell, “ATP syn­thase is one of the wonders of the molecular world.” This protein-based molecular machine is actually composed of two distinct rotary motors which are joined by a stator: As the F0 motor is powered by protons, it turns the F1 motor. This kinetic energy is used like a generator to synthesize adenosine triphosphate (ATP), the primary energy carrying molecule of cells.
  3. Bacteriorhdopsin Bacteriorhodopsin “is a compact molecular machine” that uses sunlight energy to pump pro­tons across a membrane. Embedded in the cell membrane, it consists of seven helical structures that span the mem­brane. It also contains retinal, a molecule which changes shape after absorbing light. Photons captured by retinal are forced through the seven helices to the outside of the membrane. When protons flow back through the membrane, ATP is formed.
  4. Myosin Myosin is a molecular motor that moves along a “track”—in this case actin filaments—to form the ba­sis of muscle movement or to transport cargoes within the cell. Muscles use molecular machines like myosin to “con­vert chemical energy into mechanical energy during muscle contraction.” In fact, muscle movement requires the “combined action of trillions of myosin motors.”
  5. Kinesin Motor Much like myosin, kinesin is a protein machine that binds to and carries cargoes by “crawls hand-over-hand along a microtubule” in the cell. Kinesins are powerful enough to drag large cellular organelles through the cell as well as vesicles or aid in assembly of bipolar spindles, or depolymerization of microtubules.
  6. Tim/Tom Systems Tim or Tom systems are selective protein pump machines that import proteins across the inner (Tim) and outer (Tom) membranes of mitochondria into the interior matrix of the mitochondria.
  7. Calcium Pump The calcium pump is an “amazing machine with several moving parts” that transfers calcium ions across the cell membrane. It is a machine that uses a 4-step cycle during the pump process.
  8. Cytochrome C Oxidase Cytochrome C Oxidase qualifies as a molecular machine “since part of the redox free energy is transduced into a proton electrochemical gradient.” The enzyme’s function is to carefully control the final steps of food oxidation by combining electrons with oxygen and hydrogen to form water, thereby releasing energy. It uses copper and iron atoms to aid in this process.
  9. Proteosome The proteosome is a large molecular machine whose parts must be carefully assembled in a par­ticular order. For example, the 26S proteosome has 33 distinct subunits which enable it to perform its function to de­grade and destroy proteins that have been misfolded in the cell or otherwise tagged for destruction. One paper sug­gested that a particular eukaryotic proteasome “is the core complex of an energy-dependent protein degradation machinery that equals the protein synthesis machinery in its complexity.”
  10. Cohesin Cohesin is molecular machine “multisubunit protein complex” and “a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis.”
  11. Condensin Condensin is a molecular machine that helps to condense and package chromosomes for cell repli­cation. It is a five subunit complex and is “the key molecular machine of chromosome condensation.”
  12. ClpX ClpX is a molecular machine that uses ATP to both unfold proteins and then transport unfolded proteins into another complex in the cell. It moves these proteins into the ClpP complex.
  13. Immunological Synapse The immunological synapse is a molecular machine that serves as an interface to ac­tivate T Cells. Once an immunological synapse is completely formed, T Cells are activated and proliferate, sparking a key part of the immune response.
  14. Glideosome The glideosome is a “macromolecular complex” and an “elaborate machine” whose function is to allow protozoa to rely on gliding motility over various substrates.

The author is an attorney with graduate degrees in both science and law and a staff member of the Seattle-based Discovery Institute which seeks to advance consideration of Intelligent Design theory as an alternative to Darwin­ism. You can read the original article, from which the above is an edited excerpt; along with many more examples of molecular machines in nature; and precise references for the facts stated in the article at: a/14791.



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