Repairing mutations

So duplicate genes are not macroevolution's secret laboratory.  Furthermore, everyone agrees that harmful mutations appear many, many times more often than mutations needed for new construction ever could.  Over those millions of years, slightly harmful mutations that are hidden, or not destructive enough for natural selection to remove, would also quietly accumulate.  This would produce creatures loaded up with highly polluted genes.  Survival of the barely functional?  We do not find this either because cells have mechanisms that maintain the original design of a creature within its variation boundaries, and minimize the accumulation of mutations.  These include:

• A proofreading system that catches almost all errors
• A mismatch repair system to back up the proofreading system
• Photoreactivation (light repair)
• Removal of methyl or ethyl groups by O6 - methylguanine methyltransferase
• Base excision repair
• Nucleotide excision repair
• Double-strand DNA break repair
• Recombination repair
• Error-prone bypass³⁶

Harmful mutations happen constantly.  Without repair mechanisms, life would be very short indeed and might not even get started because mutations often lead to disease, deformity, or death.  So even the earliest, "simple" creatures in the evolutionist's primeval soup or tree of life would have needed a sophisticated repair system.  But the mechanisms not only remove harmful mutations from DNA, they would also remove mutations that evolutionists believe build new parts.  The evolutionist is stuck with imagining the evolution of mechanisms that prevent evolution, all the way back to the very origin of life.

Genome size

Scientists have found that the number of genes a creature has is not a good measure of how complex it is.  For example, the human genome is 23 times larger than the fruit fly genome (3.2 billion base pairs versus 137 million), yet humans have only about 2 times the number of protein coding genes (almost 25,000 versus 13,000 according to Human Genome Project Information).  Yeast has about 6,000 genes.

		The tiny water flea Daphnia pulex has more genes than humans do; up to 39,000 at last count.Water Flea Boasts Whopper Gene Count. 5 June 2009. Science, Vol. 324, No. 5932, p. 1252.
		So does the pea aphid Acyrthosiphon pisum , with 34,600.Water Flea Boasts Whopper Gene Count. 5 June 2009. Science, Vol. 324, No. 5932, p. 1252.

The main reason for biological complexity must be in the rest of the genome, the non-coding part, which determines how those genes are used.

Junk DNA

Only a small portion of a creature's DNA is protein-coding genes (around 1.5% in humans).  In the 1970s, evolutionists began calling the rest of it "junk DNA", saying this collection of useless evolutionary debris showed there was no intelligent design involved.  Decades later, researchers are finding that the "junk" does vital work.  Some of this DNA plays a role in turning genes on and off at the right moments in a developing embryo²⁴.  Other bits separate coding and regulating sections, like punctuation marks in writing, so that DNA is not a long run-on sentence²⁵.  Other bits called Alu elements, found only in primates, can be spliced in or out during RNA processing to make different versions of the same gene.²⁶  The "junk" label discouraged research into this part of the genome for many years; who would want to waste their time studying it?

Networks

The living things of the world are extremely varied and intricately made, yet the theory of evolution has always been about simplicity: once upon a time, some chemicals assembled, began to make copies of themselves, and little by little changed into all life forms.  Evolutionists like to use the words "simply" and "merely" when telling their stories to the public.  There is certainly nothing complicated about the idea of mutation-natural selection.  However, by the year 2000, research had reached a point where a new branch of biology was needed: Systems Biology.  Discoveries in this field are the exact opposite of merely simple.  Biological systems are vastly more complex than anyone could imagine.  Some wonder if we will ever fully understand them.

A small section of a biological system in an organism, displayed as a 3D network

"To make sense of the genome, systems biologists think in terms of networks.  If two kinds of proteins or other biological molecules interact, they are connected on the network."  "These network diagrams... show how individual pathways crisscross to form a tangled web.  Each protein in a pathway can interact with molecules in other pathways, sometimes dozens of them."  Additionally, "systems biologists produce complex maps of how genes and proteins interact, and these maps help scientists analyze results from drug screening."  "Cells 'talk' to each other by passing chemical signals back and forth.  They also sense their physical surroundings through proteins on their surfaces called integrins.  All these cues serve to orient the cells in the body and inform them about how to behave so that they cooperate with the rest of the cells in the tissue."  "The cells are not complete by themselves.  They need signals from outside," says Mina J. Bissell of Lawrence Berkeley National Laboratory.  "The unit of function literally is the tissue."-- Patrick Barry. April 5, 2008. You, in a dish: cultured human cells could put lab animals out of work for chemical and drug testing. Science News, Vol. 173, No. 14, pp. 218-220.

"The interesting point coming out of all these studies is how complex these systems are; the different feedback loops and how they cross-regulate each other and adapt to perturbations are only just becoming apparent.  The simple pathway models are a gross oversimplification of what is actually happening", says Mike Tyers, a systems biologist at the University of Edinburgh, UK.-- Blow, Nathan. 16 July 2009. Untangling the protein web. Nature, Vol. 460, pp. 415-418.

This is a map of how the genes in a cell of the budding yeast Saccharomyces cerevisiaeinteract with one another.  Each color shows what a group of genes does.  Genes in these functional networks interact with other genes throughout the cell; a cell of yeast.

Costanzo, Micha
el, et al. 22 January 2010. The Genetic Landscape of a Cell.

Science, Vol. 327, No. 5964, pp. 425-431.

By 2010, real biologists had determined that gene regulatory networks (GRNs) build and operate all living things.  There are gene regulatory networks for everything that happens in them, and some networks control other networks in a chain of command.  Each species has a body plan, and it is encoded in the DNA.  "Development of the body plan is caused by the operation of GRNs".  "Embryonic development is an enormous informational transaction, in which DNA sequence data generate and guide the system-wide spatial deployment of specific cellular functions."  That is, an embryo grows because GRNs tell other GRNs what to do at the right time and place and in the right order; it is tremendously complex.  GRNs then guide the development of different types of cells, organs, and growth of the embryo into an adult.  They also control each creature's abilities and the way it responds to changes around it.  Among the most studied are sea urchins, which are low on the evolutionist's "tree of life".

An embryo has a particular growth program for the type of creature it will develop into.  Yet it is likely that all the different programs are constructed from just a few types of sub-circuits.  "Structurally similar sub-circuits, but composed of different regulatory genes" do "similar developmental jobs in different GRNs."  This discovery gives researchers hope that they can use these "modules of developmental logic function" to decipher the "enormous mazes of interconnections in system level GRNs".  You can tell what a sub-circuit does by its shape or structure.  There is a sub-circuit for each task, and GRNs are made up of sub-circuits.  The same control processes are used "throughout embryonic development because the problems that have to be solved are general: the initial spatial inputs have to be interpreted, the regulatory state then has to be locked down (the initial inputs are always transient), signals have then to be generated, other states have to be excluded, and differentiation drivers have to be activated.  It is not surprising that all this requires a lot of sequential circuitry."

GRNs in embryos "are hierarchical in their overall structure.  Their depth reflects the long sequence of regulatory steps required to complete any component of embryonic development."  A GRN might have many layers of sub-circuits or very few, depending on its job.  The last step in the chain of command is the signal for "batteries" (groups) of genes to change stem cells into specific types of cells (such as muscle, blood, nerve, etc.) at the right place.-- Davidson, Eric H. 16 December 2010. Emerging properties of animal gene regulatory networks. Nature, Vol. 468, pp. 911-920.

Some evolutionists have publicly welcomed GRNs because a change in one controller can affect many genes, and we are back to simplicity.  That is like saying a child can use Windows 7 operating system on a computer.  Just point and click with a mouse, and the computer does many complicated things.  It is simplicity itself.  So why are GRNs the death blow to evolution theory?  It took computer and software engineers decades of intelligent design to build the computer and Windows 7.  GRNs are the operating system of living things.  The theory of evolution cannot explain how gene regulatory networks came to be. As with other insurmountable problems with the theory, this one remains in the pile marked "needs further study".

Today there is an explosion of knowledge going on in the study of gene regulatory networks.  But it is not led, assisted, or even inspired by the theory of evolution.  "We have little empirical knowledge on the evolutionary history of such networks."-- Dean, Antony M., Joseph W. Thornton. September 2007. Mechanistic approaches to the study of evolution: the functional synthesis. Nature Reviews Genetics, Vol. 8, pp. 675-688.

Some of the things GRNs have been found to do:

• Specialized GRNs determine which genes are active or inactive in each part of a developing creature
• GRN sub-circuits, usually consisting of 3 to 8 regulatory genes plus the elements they regulate, perform specific functions
• Switches permit or forbid the activity of whole sub-circuits
• Gene batteries are groups of genes required for particular cell functions; they are controlled by a small set of transcriptional drivers
• Segments of DNA a few hundred base pairs long, called cis-regulatory elements, control expression of the genes near them
• Signals are deployed between one cell and another using cis-regulatory elements

-- Erwin, Douglas H., Eric H. Davidson. February 2009. The evolution of hierarchical gene regulatory networks. Nature Reviews Genetics, Vol. 10, pp. 141-148.

Mutation-natural selection could no more build the vast, intricate networks in living creatures than a beaver could build the Hoover dam.

To the next level

At this point we are light-years beyond the simplistic notions of Darwinism.  Now even systems biology is being overwhelmed.

"The protein p53, for example, was discovered in 1979."  "It soon gained notoriety as a tumor suppressor - a 'guardian of the genome' that stifles cancer growth by condemning genetically damaged cells to death.  Few proteins have been studied more than p53."

"Researchers now know that p53 binds to thousands of sites in DNA, and some of these sites are thousands of base pairs away from any genes.  It influences cell growth, death, structure and DNA repair.  It also binds to numerous other proteins."  "Through a process known as alternative splicing, p53 can take nine different forms, each of which has its own activities and chemical modifiers.  Biologists are now realizing that p53 is also involved in processes beyond cancer, such as fertility and very early embryonic development."

Research "has dismantled old ideas about signaling 'pathways', in which proteins such as p53 would trigger a defined set of downstream consequences.  'When we started out, the idea was that signaling pathways were fairly simple and linear,' says Tony Pawson, a cell biologist at the University of Toronto in Ontario.  'Now, we appreciate that the signaling information in cells is organized through networks of information rather than simple discrete pathways.  It's infinitely more complex.' "

"Systems biology was supposed to help scientists make sense of the complexity.  The hope was that by cataloguing all the interactions in the p53 network, or in a cell, or between a group of cells, then plugging them into a computational model, biologists would glean insights about how biological systems behaved."

Unfortunately, "there is no way to gather all the relevant data about each interaction".  "In many cases, the models themselves quickly become so complex that they are unlikely to reveal insights about the system, degenerating instead into mazes of interactions".  "Many of the mechanisms and principles governing inter- and intracellular behavior are still a mystery."-- Hayden, Erika Check. 1 April 2010. Life is Complicated. Nature, Vol. 464, pp. 664-667.

When cells repair damaged DNA using so-called "replicate DNA" (for making copies) or "transcribe DNA" (the first step in making a protein), the parts are rapidly assembled from a pool of parts floating in the nucleus of a cell to form "factories".  The size of a repair center is according to the amount of damage it has to repair.  "A replication factory persists for a few minutes before it disassembles.  A new factory is then assembled... immediately adjacent to the previous one".  Whether it is repair, replication, or transcription, once the job is done the "factories" disassemble and the parts float back into the pool.²⁷

Chromatin is DNA packaged into chromosomes.  Chromatin is in constant motion.³ Different sections along DNA are apparently guided to each other directly and rapidly, forming loops.¹¹  Chromatin loops are very common.  Loops range in size from thousands to hundreds-of-thousands of bases long.  Loops bring together genes and their regulators to form "transcription hubs" where transcription can occur.²⁷  "Long-range interactions can occur over very large genomic distances, up to tens of megabases".  "Interactions occur not only along chromosomes, but also between them."  "Chromosomes extensively interact with each other"³⁴, and neighboring chromosomes intermingle.²⁷

There is a "bewildering complexity in long-range communication among a variety of genomic elements across chromosomes and the genome."³⁴

The Bottom Line

Evolutionists assume evolution is true, then write endlessly about when and where it happened, rates and lineages, etc.  But if macroevolution is physically impossible in the real world, and it is, then all the rest is fantasy.  There are only two possibilities.  Either every part of every living thing arose by random chance, or an intelligence designed them.  It is now clear that the theory of evolution's only mechanism for building new parts and creatures, mutation-natural selection, is totally, utterly, pathetically inadequate.  In spite of overwhelming evidence that the theory of evolution is dead wrong, many are not ready to throw in the towel.  They desperately hope that some natural process will be found that causes things to fall together into organized complexity.  These are people of great faith.  And they are so afraid of connecting God with science that, like the Japanese Army of World War II, they would rather die than surrender.  Unfortunately, the staunchest defenders sit in places of esteem and authority as professors, scientists, and editors, and have the full faith of the news media.  The public is naturally in awe of their prestige.  But once the facts are understood it becomes obvious that the theory of evolution is long overdue for the trash can, and to perpetuate it is fraud.  Perhaps it made sense for what was known when On the Origin of Species was published in 1859, but not today.

Many scientists are with us

The only tactic left to evolutionists is to ridicule their critics as simpletons who don't understand how their pet theory really works.  Here is a link to a roster of hundreds of professionals whose advanced academic degrees certify that they thoroughly understand evolution theory.  They also have the courage to defy the high priests of academia by voluntarily adding their names to a skeptics list against Darwinism.

Some revealing quotes

Philip S. Skell, a member of the National Academy of Sciences, wrote in the August 29, 2005 edition of The Scientist: "I recently asked more than seventy eminent researchers if they would have done their work differently if they had thought Darwin's theory was wrong.  The responses were all the same: No.  I also examined the outstanding discoveries of the past century: the discovery of the double helix; the characterization of the ribosome; the mapping of genomes; research on medications and drug reactions; improvements in food production and sanitation; the development of new surgeries; and others.  I even queried biologists working in areas where one would expect the Darwinian paradigm to have most benefited research, such as the emergence of resistance to antibiotics and pesticides.  Here, as elsewhere, I found that Darwin's theory had provided no discernible guidance, but was brought in, after the breakthroughs, as an interesting narrative gloss." --Philip S. Skell. August 29, 2005. Why Do We Invoke Darwin? The Scientist, Vol. 19, No. 16, p. 10.

• Philip S. Skell was Evan Pugh Professor of Chemistry, Emeritus at Penn State University.  He is sometimes called "the father of carbene chemistry" in organic chemistry, and is widely known for the "Skell Rule", which was first applied to carbenes - the "fleeting species" of carbon.  The rule, which predicts the most probable pathway through which certain chemical compounds will be formed, found use throughout the pharmaceutical and chemical industries.  He said that during World War II "I was personally associated with an antibiotics research group, engaged in the full range of activities, from finding organisms which inhibited bacterial growth to the isolation and proof of structure of the antibiotics they produced."  Professor Skell died Nov. 21, 2010.

Ernst Chain (1906-1979) and two others were awarded the 1945 Nobel Prize for Physiology or Medicine.  Chain identified the structure of penicillin, and isolated the active substance.  He is considered to be one of the founders of the field of antibiotics.  Concerning Darwin's theory of evolution, Chain found it to be "a very feeble attempt" to explain the origin of species based on assumptions so flimsy that "it can hardly be called a theory."^A  He saw the reliance on chance mutations as a "hypothesis based on no evidence and irreconcilable with the facts."^B  He wrote:  "These classic evolutionary theories are a gross oversimplification of an immensely complex and intricate mass of facts, and it amazes me that they were swallowed so uncritically and readily, and for such a long time, by so many scientists without a murmur of protest."^B  Chain concluded that he "would rather believe in fairies than in such wild speculation" as Darwinism.^A  He was born in Berlin, Germany, and obtained his Ph.D. in biochemistry and physiology there.  He worked as a research scientist at Cambridge (also studying for a Ph.D. there), at Oxford University until 1948, and then as a professor and researcher at several other universities.  In 1938, Chain came across Alexander Fleming's 1929 paper on penicillin, and showed it to his colleague Howard Florey.  In their research, Chain isolated and purified penicillin. --Jerry Bergman, Ph.D. April 2008. Ernst Chain: Antibiotics Pioneer. Acts&Facts, Vol. 37, No. 4, pp. 10-12.

A.  Clark, R.W. 1985. The Life of Ernst Chain: Penicillin and Beyond. New York: St. Martin's Press, p. 147.

B.  Chain, E. 1970. Social Responsibility and the Scientist in Modern Western Society (Robert Waley Cohen memorial lecture). London: The Council of Christians and Jews, p. 25.

Richard C. Strohman, professor emeritus of molecular and cell biology at Berkeley, and an evolutionist, wrote in the March 1997 edition of Nature Biotechnology: "There is a striking lack of correspondence between genetic and evolutionary change.  Neo-Darwinian theory predicts a steady, slow continuous, accumulation of mutations (microevolution) that produces a progressive change in morphology leading to new species, genera, and so on (macroevolution).  But macroevolution now appears to be full of discontinuities (punctuated evolution), so we have a mismatch of some importance.  That is, the fossil record shows mostly stasis, or lack of change, in a species for many millions of years; there is no evidence there for gradual change even though, in theory, there must be a gradual accumulation of mutations at the micro level."  "We currently have no adequate explanation for stasis or for punctuated equilibrium in evolution, or for higher order regulation in cells."  "We seem to lack any scientific basis with which to explain, for example, evolution."  "Not necessarily so.  It does suggest, however, that our evolutionary theory is incomplete."  "The theory is in trouble because it insists on locating the driving force solely in random mutations."  "It is becoming clear that sequence information in DNA, by itself, contains insufficient information for determining how gene products (proteins) interact to produce a mechanism of any kind.  The reason is that the multicomponent complexes constructed from many proteins are themselves machines with rules of their own; rules not written in DNA."  "The rules... of brain formation are not reducible to genetic maps and to the rules of genetic theory.  Each higher level of organization has its own rules, and there is no continuous gradual transition from one level or hierarchy to the other."  "We have been lulled into reasoning that if the gene theory works at one level--from DNA to protein--it must work at all higher levels as well.  We have thus extended the theory of the gene to the realm of gene management.  But gene management is an entirely different process, involving interactive cellular processes that display a complexity that may only be described as transcalculational, a mathematical term for mind boggling."  "Understanding of complex function may in fact be impossible without recourse to influences outside of the genome." --Richard C. Strohman. March 1997. The coming Kuhnian revolution in biology. Nature Biotechnology, Vol. 15, pp. 194-200.

Sean B. Carroll, of the Medical Institute and Laboratory of Molecular Biology at the University of Wisconsin--Madison, wrote in a 2001 edition of Nature: "A long-standing issue in evolutionary biology is whether the processes observable in extant populations and species (microevolution) are sufficient to account for the larger-scale changes evident over longer periods of life's history (macroevolution).  Outsiders to this rich literature may be surprised that there is no consensus on this issue."-- Sean B. Carroll. 8 February 2001. Nature, Vol. 409, p. 669.

A symposium on evolution was held at the European Molecular Biology Laboratory in Heidelberg, Germany in November 2001, organized by PhD students.  The meeting report says that "the symposium ended with a panel discussion about questions of microevolution (evolution within the species) and macroevolution (evolution after speciation).  The issue at stake was whether extrapolation from the selection theory operating on organisms is sufficient to explain all patterns of macroevolution.  In other words, do we need an independent body of theory to explain the changes occurring above, as opposed to at, the species level?  There was no general agreement among the panel members.  It seems that the jury is still out on this important question."-- Gaspar Jekely. 2002. Meeting report - Evolution in a nutshell. European Molecular Biology Organization reports, Vol. 3, No. 4, pp. 307-311.

"Biology has been re-integrated twice already, first by Darwin in 1859 and then during the 'Modern Synthesis' of the 1920s and 1930s.  In both cases, the success of these syntheses rested in part on ignorance.  Charles Darwin could reasonably integrate biology in the 19^th Century on a relatively elegant evolutionary foundation partly because a great deal was not yet known about cellular and biochemical machinery."  "Like Darwin's synthesis, the form of the Modern Synthesis was shaped in part by ignorance of important features of life that were at the time unknown to science.  Specifically, the molecular biology of the cell remained largely unknown."  "The view of life that most biologists had from 1935 to 1965 was highly simplified.  Some of the assumptions at the foundation of the Modern Synthesis started to crumble in the 1970s.  Common mid-20^th Century assumptions about how cells, organisms, and species work have thus been undermined."  "This might seem like reason for despair about the future of biology, but there are two mitigations to consider.  First, this complexity was always there.  Darwin and many later biologists realized that their simple models were erected like piers over swampy ground.  They just didn't know how deep the muck was.  Second, we now have powerful genomic tools for addressing complex phenomena throughout biology."  "Some may feel that the view of life supplied by nascent 21^st Century biology is painfully complicated, if not perverse.  For our part, we think that the historical complexity and versatility that we now know to characterize life are inspiring and challenging."   "The fundamental landscape of biology is undergoing a major upheaval, much as it did in the first decades of the 20^th Century.  This upheaval will take time to fully reveal its implications."-- Michael R. Rose, Todd H. Oakley. 24 November 2007. The new biology: beyond the Modern Synthesis. Biology Direct, 2:30, 17 pages (published online).  Michael Rose is an evolutionary biologist at the University of California, Irvine.

"Origin of Life" research

The theory of evolution says life started from raw chemicals.  Evolutionists long ago handed the problem off to specialists, trusting that they would come up with something.  The specialists have spent many frustrating decades trying to figure out how DNA assembled itself.  They have two approaches to the problem, and those on one side think the other side is wrong.  Here is the essence of both views, synthesized from two research papers:

"The conceivable paths toward life's emergence have been dominated by two fundamentally different views in origin-of-life research: the genetics- or replication-first approach, and the metabolism-first scenario.  Both schools acknowledge that the critical requirement for primitive evolvable systems (in the Darwinian sense) is to solve the problems of information storage and reliable information transmission.  Disagreement starts, however, in the way information was first stored.  All present life is based on digitally encoded information."^V

The mainstream prebiotic evolutionary scenario is the "RNA world".^S  "Textbooks often assert that life began with specialized complex molecules, such as RNA, that are capable of making their own copies.  This scenario has serious difficulties, but an alternative has remained elusive."^S  "We do not know how the transition to digitally encoded information has happened in the originally inanimate world; that is, we do not know where the RNA world might have come from."^V

"An alternative appears to be necessary for the RNA-centric paradigm of the origin of life."^S "No known cellular constituent is capable of self-replication in pure form.  Even DNA is absolutely dependent on other cellular components for making its own copies."^S  "One is compelled to consider an alternative: that self-replication has never been a property of individual molecules, but rather one of molecular ensembles."^S

"The crucial origin of life question then becomes how natural selection was initiated by some molecular assortments, irrespective of their exact chemistry."^S  "Life on our planet could have begun as a random chemistry melting pot, a 'garbage-bag world' with myriads of different chemical configurations."^S  "A complex chain of evolutionary events, yet to be deciphered, could then have led to the common ancestors of today's free-living cells, and to the appearance of DNA, RNA and protein enzymes."^S

"Was a network of chemical reactions able to increase in complexity and eventually undergo Darwinian selection?"^V  "We demonstrate here that replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability."^V  "The computed population dynamics of growing noncovalent molecular assemblies that undergo splitting when a critical size is reached clearly illustrates that compositional assemblies do not evolve."^V  "We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life."^V  "We now feel compelled to abandon compositional inheritance as a jumping board toward real units of evolution."^V

S -- Segre, Daniel, Doron Lancet. 2000. Composing life. European Molecular Biology Organization (EMBO)Reports, Vol. 1, No. 3, pp. 217-222.

V -- Vasas, Vera, Eors Szathmary, Mauro Santos. January 26, 2010. Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life. Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol. 107, No. 4, pp. 1470-1475.

So neither approach works.

Here are excerpts from candid reports by two scientists who have spent many years in "origin of life" research.  These men support evolution, but insist that experimental evidence back up every claim.

This is "what has been called the NASA definition of life: Life is a self-sustained chemical system capable of undergoing Darwinian evolution."  "Richard Dawkins elaborated on this image of the earliest living entity in his book The Selfish Gene: 'At some point a particularly remarkable molecule was formed by accident.  We will call it the Replicator.  It may not have been the biggest or the most complex molecule around, but it had the extraordinary property of being able to create copies of itself.'  When Dawkins wrote these words 30 years ago, DNA was the most likely candidate for this role."  "Unfortunately... DNA replication cannot proceed without the assistance of a number of proteins".  So "which came first, the chicken or the egg?  DNA holds the recipe for protein construction.  Yet that information cannot be retrieved or copied without the assistance of proteins.  Which large molecule, then, appeared first in getting life started--proteins (the chicken) or DNA (the egg).?"

"A possible solution appeared when attention shifted to a new champion--RNA."  According to this view, "life began with the appearance of the first RNA molecule.  In a... 1986 article, Nobel Laureate Walter Gilbert of Harvard University wrote in the journal Nature: 'One can contemplate an RNA world, containing only RNA molecules that serve to catalyze the synthesis of themselves.  The first step of evolution proceeds then by RNA molecules performing the catalytic activities necessary to assemble themselves from a nucleotide soup.'  In this vision, the first self-replicating RNA that emerged from non-living matter carried out the functions now executed by RNA, DNA and proteins."  "Perhaps two-thirds of scientists publishing in the origin-of-life field... still support the idea that life began with the spontaneous formation of RNA or a related self-copying molecule."

"How did that first self-replicating RNA arise?"  Most people know of an "experiment published in 1953 by Stanley Miller.  He applied a spark discharge to a mixture of simple gases that were then thought to represent the atmosphere of the early Earth.  Two amino acids of the set of 20 used to construct proteins were formed in significant quantities, with others from that set present in small amounts."  "Some writers have presumed that all of life's building blocks could be formed with ease in Miller-type experiments and were present in meteorites and other extraterrestrial bodies.  This is not the case."

"A careful examination of the results of the analysis of several meteorites led the scientists who conducted the work to a different conclusion: inanimate nature has a bias toward the formation of molecules made of fewer rather than greater numbers of carbon atoms, and thus show no partiality in favor of creating the building blocks of our kind of life."  "RNA's building blocks, nucleotides, are complex substances as organic molecules go."  "Amino acids, such as those produced or found in these experiments, are far less complex than nucleotides".  "No nucleotides of any kind have been reported as products of spark discharge experiments or in studies of meteorites."

"To rescue the RNA-first concept from this otherwise lethal defect, its advocates have created a discipline called prebiotic synthesis.  They have attempted to show that RNA and its components can be prepared in their laboratories in a sequence of carefully controlled reactions."  Finding "a specific organic chemical in any quantity... would justify its classification as 'prebiotic,' a substance that supposedly had been proved to be present on the early Earth.  Once awarded this distinction, the chemical could then be used in pure form, in any quantity, in another prebiotic reaction.  The products of such a reaction would also be considered 'prebiotic' and employed in the next step in the sequence."  "Unfortunately, neither chemists nor laboratories were present on the early Earth to produce RNA."  "The analogy that comes to mind is that of a golfer, who having played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence.  He had demonstrated the possibility of the event; it was only necessary to presume that some combination of natural forces (earthquakes, winds, tornadoes and floods, for example) could produce the same result, given enough time."

"Many chemists, confronted with these difficulties, have fled the RNA-first hypothesis as if it were a building on fire.  One group, however, still captured by the vision of the self-copying molecule, has opted for an exit that leads to similar hazards.  In these revised theories, a simpler replicator arose first and governed life in a 'pre-RNA world.'  Variations have been proposed in which the bases, the sugar or the entire backbone of RNA have been replaced by simpler substances, more accessible to prebiotic syntheses.  Presumably, this first replicator would also have the catalytic capabilities of RNA.  Because no trace of this hypothetical primal replicator and catalyst has been recognized so far in modern biology, RNA must have completely taken over all of its functions at some point following its emergence."

"Further, the spontaneous appearance of any such replicator without the assistance of a chemist faces implausibilities that dwarf those involved in the preparation of a mere nucleotide soup.  Let us presume that a soup enriched in the building blocks of all of these proposed replicators has somehow been assembled, under conditions that favor their connection into chains.  They would be accompanied by hordes of defective building blocks, the inclusion of which would ruin the ability of the chain to act as a replicator."  "There is no reason to presume that an indifferent nature would not combine units at random".

"Probability calculations could be made, but I prefer a variation on a much-used analogy.  Picture a gorilla (very long arms are needed) at an immense keyboard connected to a word processor.  The keyboard contains not only the symbols used in English and European languages but also a huge excess drawn from every other known language and all of the symbol sets stored in a typical computer.  The chances for the spontaneous assembly of a replicator in the pool I described above can be compared to those of the gorilla composing, in English, a coherent recipe for the preparation of chili con carne.  With similar considerations in mind, Gerald F. Joyce of the Scripps Research Institute and Leslie Orgel of the Salk Institute concluded that the spontaneous appearance of RNA chains on the lifeless Earth 'would have been a near miracle.'  I would extend this conclusion to all of the proposed RNA substitutes that I mentioned above."  "Nobel Laureate Christian de Duve has called for 'a rejection of improbabilities so incommensurably high that they can only be called miracles, phenomena that fall outside the scope of scientific inquiry.'  DNA, RNA, proteins and other elaborate large molecules must then be set aside as participants in the origin of life."

What is left?  Theories that "employ a thermodynamic rather than a genetic definition of life, under a scheme put forth by Carl Sagan in the Encyclopedia Britannica: A localized region which increases in order (decreases in entropy) through cycles driven by an energy flow would be considered alive."  "I estimate that about a third of the chemists involved in the study of the origin of life subscribe to theories based on this idea."

It requires: "1) A boundary... to separate life from non-life."  "2) An energy source".  "3) A coupling mechanism must link the release of energy to the organization process that produces and sustains life.  The release of energy does not necessarily produce a useful result.  Chemical energy is released when gasoline is burned within the cylinders of my automobile, but the vehicle will not move unless that energy is used to turn the wheels.  A mechanical connection, or coupling, is required."  "4) A chemical network must be formed, to permit adaptation and evolution" "on a path that leads to increased organization."  "5) The network must grow and reproduce."  "We can imagine, on the early Earth, a situation where many startups of this type occur, involving many alternative driver reactions and external energy sources.  Finally, a particularly hardy one would take root and sustain itself."  "A system of reproduction must eventually develop."  "Once independent units were established, they could evolve in different ways and compete with one another for raw materials; we would have made the transition from life that emerges from nonliving matter through the action of an available energy source to life that adapts to its environment by Darwinian evolution."  "Many further steps in evolution would be needed to 'invent' the elaborate mechanisms for replication and specific protein synthesis that we observe in life today."  They "would not reveal the specific events that led to the familiar DNA-RNA-protein-based organisms of today."

"Systems of the type I have described usually have been classified under the heading 'metabolism first', which implies that they do not contain a mechanism for heredity.  In other words, they contain no obvious molecule or structure that allows the information stored in them (their heredity) to be duplicated and passed on to their descendants."  "Over the years, many theoretical papers have advanced particular metabolism first schemes, but relatively little experimental work has been presented in support of them."  "They have not yet demonstrated the operation of a complete cycle or its ability to sustain itself and undergo further evolution.  A 'smoking gun' experiment displaying those three features is needed to establish the validity of the small molecule approach."

Shapiro, Robert. June 2007. A Simpler Origin for Life. Scientific American, Vol. 296, pp. 24-31.

Robert Shapiro, Ph.D. Harvard, is professor emeritus of chemistry and senior research scientist at New York University.  He is author or co-author of over 125 publications, primarily in the area of DNA chemistry.  In 2004 he was awarded the Trotter Prize in Information, Complexity and Inference.  Shapiro has been involved in the search for origin of life mechanisms, and has written four books on the subject for the general public.

"The feasibility of any particular proposed prebiotic cycle must depend on arguments about chemical plausibility, rather than on a decision about logical possibility."  The metabolic cycles that have been identified by biochemists are of two kinds: simple cycles and autocatalytic cycles.  The citric acid cycle" is an example of a simple cycle.  "The reverse citric acid cycle" is an example of an autocatalytic cycle.  "Each molecule of citric acid introduced into the cycle results... in the generation of two molecules of citric acid."  "That is why the cycle is described as autocatalytic."  "The proposal that the reverse citric acid cycle operated... on the primitive Earth has been a prominent feature of some scenarios for the origin of life."

"A different kind of autocatalytic cycle, which has no analog in biochemistry, has been hypothesized by Stuart Kauffman to self-organize spontaneously whenever amino acids condense together to form peptides."  "Could prebiotic molecules and catalysts plausibly have the attributes... to make the self-organization of the cycles possible?"

"The identification of a cycle of plausible prebiotic reactions is a necessary but not a sufficient step toward the formulation of a plausible self-organizing prebiotic cycle.  The next, and more difficult step, is justifying the exclusion of side reactions that would disrupt the cycle."  "It is not completely impossible that sufficiently specific mineral catalysts exist for each of the reactions of the reverse citric acid cycle, but the chance of a full set of such catalysts occurring at a single locality on the primitive Earth in the absence of catalysts for disruptive side reactions seems remote in the extreme."

"It has sometimes been implied or claimed that [autocatalytic] cycles are not only stable, but also are capable of evolving to form nonenzymatic networks of great complexity.  Genetic materials are then seen as late additions to already fairly complex evolved life forms.  According to this view, a genetic material merely adds stability to systems that already have a substantial 'information content'. "

"One way of achieving something useful might be to use one of the constituents of the core cycle as the starting point of a second independent autocatalytic cycle."  "Another suggestion that might be explored is the possibility of a side reaction generating a catalyst for one of the reactions of the core cycle."  "However, neither of these possibilities, nor any others with which I am familiar explains how a complex, interconnected family of cycles capable of evolution could arise or why it should be stable."  "What is essential, therefore, is a reasonably detailed description, hopefully supported by experimental evidence, of how an evolvable family of cycles might operate."  "Without such a description, acceptance of the possibility of complex nonenzymatic cyclic organizations that are capable of evolution can only be based on faith, a notoriously dangerous route to scientific progress."

"Kauffman takes it for granted that if it is possible to write down on paper a closed peptide cycle and a set of catalyzed ligations leading from monomeric amino acids to the peptides of the cycle, then that cycle would self-organize spontaneously and come to dominate the chemistry of a reaction system.  This... is unlikely because peptide molecules do not have the properties that Kauffman assigns to them."  "I have also explored a number of alternative systems with different numbers of amino acids or with inputs of random families of short peptides, and I find that they all encounter similar or more severe difficulties."

"Kauffman assumes that, in sufficiently concentrated solution, the naturally occurring amino acids or some subset of them would condense spontaneously to form a mixture of long peptides in substantial yield.  In practice, this would not happen."  "The catalytic properties of enzymes are remarkable.  They not only accelerate reaction rates by many orders of magnitude, but they also discriminate between potential substrates that differ very slightly in structure.  Would one expect similar discrimination in the catalytic potential of peptides of length ten or less?  The answer is clearly 'no', and it is this conclusion that ultimately undermines the peptide cycle theory."

"Protein catalysis is dependent on the stable three-dimensional structures of enzymes and enzyme-substrate complexes.  Highly specific catalytic activity could only be expected from short peptides if they, too, adopted stable structures."  "In fact, short peptides rarely form stable structures, and when they do, the structures are only marginally stable.  The synthesis of a decapeptide that would catalyze the ligation in the correct order of two particular pentapeptides out of a mixture of ten pentapeptides that are required to form the five cycle components, while failing to bring about any of the other possible ligations, would present an extremely difficult challenge to peptide chemistry.  It seems certain that the additional requirement that this peptide should also catalyze specifically many of the reactions leading from amino acids to the pentamer precursors of the decamers of the cycle could never be met.  Of course, the decamers need not be formed only from pairs of pentamers, but the difficulties are no less severe for more complex synthetic networks.  There are a number of possible ways in which this difficulty might be circumvented, but none seems relevant to the origin of life."  "It is unlikely, therefore, that Kauffman's theory describes any system relevant to the origin of life."

"It is essential to subject metabolist proposals to the same kind of detailed examination and criticism that has rightly been applied to genetic theories."  "Because little experimental work has been attempted, appraisal must be based on chemical plausibility."  "The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to 'life-like' complexity.  The most serious challenge to proponents of metabolic cycle theories--the problems presented by the lack of specificity of most nonenzymatic catalysts--has, in general, not been appreciated.  If it has, it has been ignored."

"Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories: they must stand on their own."  "Experimental proof that such cycles are stable against the challenge of side reactions is even more important."  "The prebiotic syntheses that have been investigated experimentally almost always lead to the formation of complex mixtures.  Proposed polymer replication schemes are unlikely to succeed except with reasonably pure input monomers.  No solution of the origin-of-life problem will be possible until the gap between the two kinds of chemistry is closed."  "Solutions offered by supporters of geneticist or metabolist scenarios that are dependent on 'if pigs could fly' hypothetical chemistry are unlikely to help."

Orgel, Leslie E. January 2008. The Implausibility of Metabolic Cycles on the Prebiotic Earth. Public Library of Science (PLoS) Biology, Vol. 6, No. 1, e18, pp. 5-13.

Leslie E. Orgel, Ph.D. Oxford, was a biochemist who studied life on primitive Earth.  He conducted research at Cambridge, the University of Chicago, the California Institute of Technology, and later joined the Chemical Evolution Laboratory of the Salk Institute for Biological Studies in San Diego, California.  He died at age 80 in October 2007.  The above article was published posthumously.

After the "tree of life"

In a paper about bacteria, two evolutionary biologists write, "we cannot rely exclusively on traditional genealogical relationships."  "A single taxonomy will be likely to provide an overly coarse picture".  It should be replaced by "more taxonomies based on real biological processes".  "Discarding all but one of these process-based taxonomies would be comparable to reducing a person's identity to a single aspect of his or her life, even though he or she might have an effective role in many organizations: professional, artistic, sports, family and so on.  To avoid overlooking any of the natural groups, it seems legitimate to propose - rather than a single taxonomy of microbial species - many taxonomies".  "We suggest giving up the unique hierarchy as the reference classification system and instead encourage the production of a comprehensive interactive database in which an individual could possibly belong to overlapping taxonomical groups."  "Any organism can then be characterized by many names because it can belong to more than one group at once."

Bapteste, Eric, Yan Boucher. 2008. Lateral gene transfer challenges principles of microbial systematics. Trends in Microbiology, Vol. 16, No. 5, pp. 200-207.

Epigenetics (meaning "above" genetics, as in controlling elements)

Evolutionists are starting to turn to epigenetics to explain macroevolutionary changes.  However, most of them do not know much about molecular biology, and they are scrambling to catch up.  "During the twentieth century, evolutionary and molecular biology diverged".  "Few scientists were trained in both fields, and many biology departments were split up."  "Most evolutionary biologists emphasize... variation".  "Inferences about the historical mechanisms that generate variation are usually drawn from patterns of association".  "The weakness is that statistical associations are not reliable indicators of causality."  "Claims that are based solely on associations remain standard in the field."  "Evolutionary biologists will need to be trained in molecular biology".-- Dean, Antony M., Joseph W. Thornton. September 2007. Mechanistic approaches to the study of evolution: the functional synthesis. Nature Reviews Genetics, Vol. 8, pp. 675-688.

Here is some of what real molecular biologists have learned, beginning with a March 2008 report in Science News magazine: "Many people regard ribonucleic acid, as RNA is formally known, as 'just a middleman between DNA and protein,' says Claes Wahlestedt, a neuroscientist and genome researcher at the Scripps Research Institute in Jupiter, Fla.  Shuttling genetic information from DNA to a cell's protein factories has long been recognized as RNA's day job, summarized" as "DNA makes RNA makes protein."  "Some researchers estimate that as much as 98 percent of the human genome is copied into RNA, says Sofie Salama of the University of California, Santa Cruz."  "Initial observations of the genome showed islands of protein-coding genes separated by vast oceans of DNA--sometimes called junk DNA--where nothing happened.  That would mean that only about 2 percent of the human genome is transcribed into RNA.  But recent efforts to map all of the RNA transcripts show that virtually every base pair of DNA in the human genome is copied into at least one RNA molecule."

"More than 20 classes of noncoding RNA have been discovered in the past decade.  Many of these RNAs are much smaller than their protein-coding cousins, the messenger RNAs.  Some noncoding RNAs contain a mere 20 nucleotides, the chemical units corresponding to letters in the genetic alphabet.  Scientists used to throw away such short bits of RNA, thinking the tiny pieces were nothing more than breakdown products of larger molecules--basically garbage, Wahlestedt says."

"Researchers now know that noncoding RNAs get involved in virtually everything that happens in or to a cell, says Georges St. Laurent III, a computational and molecular biologist at George Washington University in Washington, D.C."  "They monitor temperature, chemical conditions, electrical currents, and other signals from the environment and then tell the cell how to respond."

"One class of noncoding RNAs, known as microRNAs, modulates production of proteins.  MicroRNAs get their name from their minuscule size--most are only about 22 nucleotides long.  These short pieces of RNA find and bind to complementary sequences in messenger RNAs.  Usually that binding causes the ribosome, the protein-building machinery in a cell, to grind to a halt.  The ribosome remains paused until other signals allow it to resume making protein or until the RNA message is destroyed."  " 'It's not only important that you make a particular protein, but when and where you make it,' Salama says."-- Tina Hesman Saey. March 1, 2008. Micromanagers: New classes of RNAs emerge as key players in the brain. Science News, Vol. 173, No. 9, pp. 136-137.

Non-coding RNAs have risen from "junk" to "drivers of complexity".³⁴  "Sequencing the genomes of 85 species has revealed that in any given organism, increasing biological complexity is correlated with an increasing number of non-protein-coding DNA sequences and not, as previously assumed, with an increasing number of protein-coding genes."³⁴ "The sheer number of non-coding RNAs is estimated in the 100s of thousands."¹⁵  "It is clear that tens of thousands may operate within a cell".³⁴

"Interference and activation can be caused by the same transcript".⁴  "A large part of the transcriptional activity in the human genome is derived from repeat sequences".³⁴  "Repeat elements... occupy 40-45% of a typical mammalian genome".⁴  "Alu repetitive elements constitute 10% of the human genome".²⁶  "Repeat elements, such as the Alu family in humans and B2 in mice have provided regulatory signals for RNA PolII transcription."⁷ "Some of the Alu elements... may have functions in stress response, chromatin organization or signaling events in the early embryo.  Alu transcripts are... activated by heat shock and DNA damaging agents".³⁴

There are levels of non-coding RNA regulation that have yet to be discovered.³⁴  Studying the old "junk" transcripts can lead to understanding hidden layers of cell regulation and how deregulation can lead to the understanding of human disease.³⁴  "The scientific community is getting more aware of the importance of the formerly abandoned 'junk' DNA.  What we have learned so far is likely just the tip of the iceberg."³⁴

It is clear that biological complexity depends less on gene number and more on how those genes are used.  Researchers are realizing that regulation is on multiple levels²⁷; there are intricate feedback loops.⁶  Stretches of DNA can be inactivated by attaching methyl groups.  Tiny embryos need to grow according to a body plan organized in steps that have to happen at the right time in the right sequence.  Their cells use timers and spatial signals to guide their growth.  For example, a signal chemical is made at one end of an embryo and spreads out.  Cells act according to how much signal chemical reaches them.  Signal chemicals spreading from opposite ends of an embryo can interact to coordinate construction.²³

In small genomes, such as yeast, the parts of DNA that regulate a gene are next to the gene.  In more complex genomes, such as human and mouse, they can be far apart.  Cells have ways, still unknown, of moving sections of chromosomes next to each other to get the right parts together to control gene expression.¹¹  This happens constantly.

To respond to a rapidly changing environment, a creature's genes have to be turned on and off in a highly coordinated way.  The genetic network must be stable under a broad range of conditions, but flexible enough to recognize and respond to important signals when things around it change.  This operating at the brink of order and chaos is well known to systems scientists.  They call such systems critical.  This property has now been recognized in plants, animals, and microbes.  It allows them to quickly detect and respond to external stimuli, small or large.⁴

In another surprise to evolutionists, genes they have long called vestigial junk have a clear purpose.  Some genes are not transcribed into proteins, yet they seem related to working genes.  So evolutionists figured these were leftover copying mistakes, called them pseudogenes (fake genes), and ignored them.  Researchers studying cancer finally took a look at a pseudogene in action, and found that it competed with its working gene for the same non-coding regulatory RNA.  Thus the gene and pseudogene act as decoys for one another, and affect the regulation of other transcripts.  The pseudogene "is not a non-functional relic, but a modulator of gene expression."  This "could have major implications for understanding mechanisms of disease, and of cancer in particular."  "The authors find similar associations between other well-known cancer-associated genes and their corresponding pseudogenes."

Poliseno, Laura, Leonardo Salmena, Jiangwen Zhang, Brett Carver, William J. Haveman, Pier Paolo Pandolfi. 24 June 2010. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, Vol. 465, pp. 1033-1038.
Rigoutsos, Isidore, Frank Furnari. 24 June 2010. Decoy for microRNAs. News & Views, Nature, Vol. 465, pp. 1016-1017.