SanGene 09-01-006
	Genetic Entropy & The Mystery of the Genome Dr. J. C. Sanford Elim Publishing, 2005, 208 pp., ISBN 1-59919-002-8

Dr. John Sanford is a semi-retired researcher and plant geneticist from Cornell University.

The complexity of a bacterium, the simplest form of life, is as great as that of the space shuttle. And the jump in complexity from a bacterium to a human is as great as from a little red wagon to the space shuttle.

So far we have discovered only the first dimension of this "book of life," a linear sequence of 4 types of nucleotides. Small clusters, or motifs, of these four molecular letters make up the words which combine to form genes, the chapters, which combine to form chromosomes, the volumes, which combine to form the whole genome, the entire library of instructions for life.

"The genome is the instruction manual which specifies life." "An organism's genome is the sum total of all its genetic parts, including all its chromosomes, genes, and nucleotides." (1)

A complete human genome consists of two sets of 3 billion individual 'letters' each. A fraction of this library encodes 100,000 human proteins. (2) "Each of these protein and RNA molecules are essentially miniature machines, each with hundreds of component parts, each with its own exquisite complexity, design and function." (3)

"The genome's set of instructions is not a simple, static, linear array of letters; but is dynamic, self-regulating, and multi-dimensional. There is no human information system that can even begin to compare to it." (4) "Each human body contains a 'galaxy' of cells (more than 100 trillion), and every one of these cells has a complete set of instructions and its own highly prescribed duties." Carl Sagan said each cell contains more information than the Library of Congress. (4)

"The standard answer to the origin of biological information is that mutation combined with selection have created all biological information." This the Primary Axiom of biological evolution. (5) "No intelligence is involved in this scenario." Natural selection is a term for a blind and purposeless process whereby some things reproduce more than others. (8-9)

"An Axiom is an untestable concept, which is accepted by faith because it seems so obviously true to all reasonable parties. On this basis, it is accepted as an Absolute Truth." (5) This book questions whether we should accept today's Primary Axiom. (5)

"Mutations are complex and happen at the molecular level, but selection can only be carried out on the level of the whole organism." (6)

"Random mutations consistently destroy information." (15) Random variation is like what happens to your car over time: dings, rust and breakage. Typographical errors do not improve a student's paper and throwing rocks does not improve glass houses. Alternative, designed variations may improve your car, your paper, or your house. "Part of the Primary Axiom is that all genetic variation must come from random mutations, since no genetic variation by design is allowed." However, it can reasonably be argued that random mutations never improve quality. (16) "I am still not convinced there is a single, crystal-clear example of a known mutation which unambiguously created information. Some random changes may be beneficial (like a broken car alarm to a thief), and some plants may be more useful or pretty because of a loss of a cell function, for example. But no new information is created. (17)

"I have seen estimates of the ratio of deleterious-to-beneficial mutations which range from one thousand to one, up to one million to one." The actual rate is so low as to thwart any real measurement. (24) Even when a mutation is beneficial, it usually represents part of an over-all erosion of information. (27)

Human mutation rates are much too high. (33) It is at least 100 nucleotide substitutions (misspellings) per person per generation. (34) "It is becoming increasingly clear that most, or all, of the genome is functional. Therefore, most, or all, mutations in the genome must be deleterious." (39) With 6 billion people adding 100 new mutations each, our generation alone has added roughly 600 billion new mutations to the human race. This degenerative process will continue. We are on a downward slide. (40) "Mutational meltdown is recognized as an immediate threat to all of today's endangered species. The same process appears to potentially be a theoretical threat for mankind. What can stop this process?" (41) The decline in our species fitness is estimated at 1-2% per generation. (45)

Natural selection is a very real phenomenon and it has very real capabilities and very real limitations. (46) "Selection acts on the level of the organism, not on the level of the nucleotide." (54)

"There must be a vanishingly small correlation between any given nucleotide (a single molecule), and a whole organism's probability of reproductive success!" "It is a little like trying to select for a specific soldier, based upon the performance of his army." (49) For analogy, suppose each student is given a biochemistry text with random misspellings, duplications, and deletions. At the end of the course, you save the textbooks of those students who got the best grades. The noise (other factors) will easily override the effect of the textbook errors. (50) The textbooks will obviously degrade over time and average student scores will eventually go down. While such a blind process will never improve textbooks, the Primary Axiom claims that this mutation/selection process wrote the textbook in the first place. There was never any intelligent agent acting as author or editor. (51)

Selection is only possible to the extent that there is residual excess population. "Fitness…is actually the real trait that natural selection always acts upon, and this very fundamental trait is actually very poorly inherited." (59) Environmental factors are much more important than genetic factors.

Genetic selection works. My career in science involved use of artificial selection as a plant breeder. But both natural and artificial selection have very limited ranges of operation. (63) "Selection works on the genic level, but fails at the genomic level." (64)

As a population we carry many trillions of deleterious mutations. (71) They will continue to accumulate and the species must degenerate. (72) The mutations of nucleotides result in gradual erosion of information. (73) "If we start with a very long and complex written message (i.e. an encyclopedia), and we start to introduce typographical errors, most of the individual errors will only have an extremely trivial effect on the total message. Individually, they are truly insignificant. But if this process is not halted, eventually the message will become corrupted, and it will eventually be completely lost." (73)

"While selection is essential for slowing down degeneration, no form of selection can actually halt it." (83)

"A very weak signal is easily destroyed by any amount of noise." (90) "In the big picture, noise will consistently outweigh the effects of individual nucleotides. This is a primary reason why selection works on the level of the gene, but fails on the level of the genome." (90) "Total fitness combines all the different types of noise from all the different aspects of the individual." (91) "Low heritability means that selecting away bad phenotypes does very little to actually eliminate bad genotypes." (91)

For example, "consider seeds from a cottonwood tree. Some seeds will land on fertile ground ideal for growth, with abundant moisture, few weeds, etc. But most seeds will land on placers that are too dry, too wet, too many weeds, too much shade, too many people, etc. The result will be great diversity in the health and vigor of the resulting trees, and huge differences in their survival and reproduction. But almost all of this 'natural selection for the fittest', will really only be selection of the luckiest - not the genetically superior." (91)

"If noise routinely over-rides selection, then this makes long-term evolution impossible…." (99)

"If the genome is actually degenerating, it is bad news for the long-term future of the human race. It is also bad news for evolutionary theory. If mutation/selection cannot preserve the information already within the genome, it is difficult to imagine how it could have created all that information in the first place! We cannot rationally speak of genome-building when there is a net loss of information every generation!" (105-6)

In The Descent of Man, Darwin contended for superior races, ushering in an era of racism working its way out in Hitler's Germany. Prior to WWII many nations had government-directed eugenics programs that force sterilized the 'unfit,' and promoted abortion/fertility-control for the underclasses. The eugenic's vision is an insidious delusion. (116-17) "Eugenics has from its inception been a racist concept, and has always been driven by the Primary Axiom. Eugenics is not genetically sound. Furthermore, it is tightly linked with authoritarian government, elitist philosophy, suppression of personal rights, and violation of human dignity." (118)

"In plant genetic improvement, when a species is easily propagated clonally, clonal selection provides the surest and fastest way to improve a population. Just choose the best individuals, and multiply! It is about that simple." (118)

However, within any clonal line, even the best sub-clones will accumulate mutations over time. Even selection does not stop the decline. All change is downward. Each cell division adds mutations. Net information always declines. "Cloned animals routinely display immediate and severe genetic damage. It is as if they are "pre-aged." (119)

"New mutations occur in every cell, at the rate of roughly one mutation every cell division. Therefore, essentially every single cell in our body is unique. For these reasons every human clone will always be inferior to the mature 'source individual' from which they were cloned. Such a clone will in a sense be pre-aged - having the original mutational load of the source individual, plus the mutational load that has accumulated during that person's growth and aging." "There are powerful moral, social, and genetic arguments against cloning." (120)

Genetic entropy, the degeneration of the genome: we experience it on a personal level; we see it all around us; and it is why we are all individually in the process of dying. (121)

Can mutation/selection create a new gene? No. "To create a new function, we will need to select for our first beneficial mutation, but we can only define that new nucleotide's value in relation to its neighbors. Yet to create any new function, we are going to have to be changing most of those neighbors also! We create a circular path for ourselves - we will keep destroying the 'context' we are trying to build upon. This problem of the fundamental inter-relationship of nucleotides is called epistasis. True epistasis is essentially infinitely complex, and virtually impossible to analyze, which is why geneticists have always conveniently ignored it. Such bewildering complexity is exactly why language (including genetic language) can never be the product of chance, but requires intelligent design. The genome is literally a book, written literally in a language, and short sequences are literally sentences. Having random letters fall into place to make a single meaningful sentence, by accident, is numerically not feasible. The same is true for any functional strings of nucleotides. … A pre-existing 'concept' is required as a framework upon which a sentence or a functional sequence must be built. Such a concept can only pre-exist within the 'mind of the author". Starting from the very first mutation, we have a fundamental problem - even in trying to define what our first desired beneficial mutation should be!" (124-25)

Man and chimp differ at roughly 150 million nucleotide positions, which are attributed to at least 40 million hypothetical mutations. (130)

"Most DNA sequences are poly-functional, and so must also be poly-constrained." The DNA has meaning on several levels. "For example, imagine a sentence which has a very specific message in its normal form, but has an equally coherent message when read backwards. Now let's suppose that it also has a third message when reading every other letter, and a fourth message when a simple encryption program is used to translate it. Such a message would be poly-functional and poly-constrained. We know that misspelling in a normal sentence will not normally improve the message - but at least this would be possible. However, a poly-constrained message is fascinating, in that it cannot be improved - it can only degenerate." (131) "Changing anything seems to potentially change everything!" (133)

The author provides several additional arguments along separate lines, but the conclusion is the same. Even though we know that 'micro-evolution' (adaptive selection) does happen, the genome must have been designed and could not have evolved. "When we see adaptive selection occurring, we are usually witnessing segregation and recombination of useful variants of genes and gene components - which were designed to segregate and recombine in the first place. We are not usually seeing the result of random mutations - which are consistently deleterious." (139-40)

"Mutational entropy appears to be so strong within large genomes that selection can not reverse it. … I have termed this fundamental problem Genetic Entropy. Genetic Entropy is not a starting axiomatic position - rather it is a logical conclusion derived from careful analysis of how selection really operates." (144)

"Selection occurs on the level of the whole organism, and cannot stop the loss of information due to mutation, which is immeasurably complex, and is happening on the molecular level. It is like trying to fix a computer with a hammer - the microscopic complexity of the computer makes the hammer largely irrelevant. Likewise, the microscopic complexity of genomic mutation makes selection on the level of the whole individual largely irrelevant." (144)

"If the Primary Axiom is wrong, then our basic understanding of life history is also wrong. If the genome is degenerating, then our species is not evolving, but is essentially 'aging.'" There appears to be a close parallel between the aging of a species and the aging of an individual. Both seem to involve the progressive accumulation of mutations." "Genetic damage results in aging, and aging shortens lifespan. This is true for the individual and for the population. Logically we should conclude that if all of this is true, then at some time in the past - there must have been a time when there was less genetic damage in the genome, and thus longer lives, and less deleterious effects from inbreeding. (147)

"Information theory clearly indicates that information and information systems arise only by intelligence, and are only preserved by intelligence." (150) "Information's fundamental nature is to degenerate, and this reality is reflected all around us…. The reason our information systems do not degenerate even more rapidly is because of our elaborate, intelligently-designed systems to stabilize and preserve information." (151)

Postlude - There is a hope. 153 ff.

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