A Book Review and Summary of John C. Sanford’s Genetic Entropy and the Mystery of the Genome

From Issue: R&R – June 2013

Dr. John Sanford is a plant geneticist and inventor who conducted research at Cornell University for more than 25 years. He is best known for significant contributions to the field of transgenic crops, including the invention of the biolistic process (“gene gun”). Like many in his profession, he was fully invested in what he terms the “Primary Axiom” of modern science, namely that “man is merely the product of random mutations plus natural selection” (Sanford, 2008, p. v, italics in orig.). He argues that this cornerstone of modern Darwinism is almost universally accepted and rarely, if ever, questioned. In Genetic Entropy and the Mystery of the Genome, Sanford proceeds, not only to question the Primary Axiom, but to expose completely the faulty genetic framework upon which the ideology is built.

In the first portion of the book, Sanford builds an analogy for the reader to make complex genetic concepts more palatable to non-scientists. He uses the analogy of comparing our genome—the sum total of all of our genetic makeup—with an instruction manual. The DNA sequences that make up our genes, gene regulatory elements, chromosomes, etc., are compared with letters, words, chapters, and volumes. [NOTE: The term “gene” is not to be taken as synonymous with “trait.” Mendelian genetics dealt in “traits” (e.g., blue eyes) that were defined as “genes.” Our modern understanding of genetics demonstrates that while many genes impact phenotype (observable traits), genes are not the same as traits.] He builds on this analogy throughout the book using several powerful illustrations.

When we view the genome as an instruction manual, it is not hard to imagine how instructions in that manual may change simply by randomly changing letters in the manual. These changes are analogous to the random changes in our genome that are referred to as mutations. Mutations can be as simple as a single “letter” (i.e., a nucleotide) being changed or as major as the loss or duplication of an entire “book” (i.e., a chromosome). Our genome includes six billion “letters” split into 46 “volumes” (in a typical body cell; 23 chromosomes in reproductive cells). It is clear, though, that randomly changing letters in an instruction manual would not provide new and useful information.

Sanford argues that, based upon modern scientific evidence and the calculations of population geneticists (who are almost exclusively evolutionists), mutations are occurring at an alarmingly high rate in our genome and that the vast majority of all mutations are either harmful or “nearly-neutral” (meaning a loss for the organism or having no discernible fitness gain). Importantly, Sanford also establishes the extreme rarity of any type of beneficial mutations in comparison with harmful or “nearly-neutral” mutations. Indeed, “beneficial” mutations are so exceedingly rare as to not contribute in any meaningful way. [NOTE: “Beneficial” mutations do not necessarily result from a gain in information, but instead, these changes predominantly involve a net loss of function to the organism, which is also not helpful to the Primary Axiom; see Behe, 2010, pp. 419-445.] Sanford concludes that the frequency and generally harmful or neutral nature of mutations prevents them from being useful to any scheme of random evolution. 

Using his analogy, imagine a manual for assembling a child’s wagon. Would randomly changing letters in the manual improve the manual? Would duplicating sections of the manual improve it? Clearly these types of changes would destroy information rather than create new information (having two copies of the same information is not necessarily of benefit, since there is no real mechanism to preserve one copy while mutating another). But Sanford extends the analogy further. He suggests that the Primary Axiom assumes that such random changes not only could change the wagon, but these random “mutations” would evolve the wagon into a car and eventually a plane, and then even a space shuttle. No one would argue that random changes in the manual for a wagon would eventually give rise to instructions for a space shuttle. However, Sanford argues this is exactly the situation with regard to our genome. If we regard “early” life forms in an evolutionary context as being the wagon, humans would easily be a space shuttle by comparison!

In the next section of the book, Sanford examines natural selection and asks whether “nature” can “select” in favor of the exceedingly rare “beneficial” mutations and against the deleterious mutations. The concept of natural selection is generally that the organisms that are best adapted to their environment will survive and reproduce, while the less fit will not. Sanford points out that this may be the case with some organisms, but more commonly, selection involves chance and luck. But could this process select against harmful mutations and allow less harmful or even beneficial mutations to thrive? According to Sanford, there are significant challenges to this notion. One major issue is the cost of selection. The cost of selection means that a portion of a population must be “spent” (i.e., removed) in order to “pay” for the selection process. To put this idea in human terms, what percentage of the population could be removed (or kept from reproducing) in order to promote selection? The numbers are exceedingly high according to Sanford—possibly higher than 50%—which would be completely unrealistic in any society today. Another issue is the “blind” nature of the process. Nature cannot “see” what potential future organisms could exist, and therefore, there is no means for selecting for or against traits to achieve any future goals. Sanford concludes that selection cannot overcome the accumulation of harmful mutations and has no real power to keep “beneficial” mutations around, due to the extreme rarity of those mutations and the fact that selection is blind. Thus, even with the ability to select—artificially or otherwise—the accumulation of mutations continues unabated.

In the final section of the book, Sanford illustrates the dire situation of the human genome. Imagine an instruction manual of tens of thousands of pages in which random changes have been made every time it is copied. Who would trust such a manual? How many changes would it take to make the manual unusable? How long before the manual no longer makes a functional product? It is a testimony to the nature of our genome that we are still alive in spite of the level of decay. Again, Sanford points to the accumulation of deleterious mutations and argues that our genomes are not evolving to something greater; we are decaying and degenerating. In other words, our genomes at one point were in far better shape than they are at present. The decay process has taken a huge toll. This process he terms “genetic entropy.” He suggests that this decay trend is not only real, but it is an inevitable result of the random, natural accumulation of mutations in our genome. Thus, not only do mutations lead to decay, they do not lead to any meaningful increase in information—which is absolutely required by the Primary Axiom. In order for organisms to evolve from one form to another, new genetic information is needed in order to provide “instructions” for building the proteins and other features of the organism. Sanford clearly establishes that any expectation of getting new, useful information from these random processes is a completely blind trust in an impotent process. His book also provides an appendix with several more arguments against the Primary Axiom, along with answers to some counterarguments.

In conclusion, Sanford’s book builds a strong case against the Primary Axiom using modern scientific information combined with powerful, yet simple, logic. His arguments are solid but written on a level that can be understood by students and non-scientists. He clarifies several misconceptions about mutations, natural selection, and the overall decay of the genome. He accurately describes the concept and reality of genetic entropy, and he concludes from that principle our dependence upon the One who designed everything. Rather than viewing life as a purposeless by-product of the Primary Axiom, Sanford argues that genetic entropy points us to our need for and reliance upon God as the Creator. Perhaps this system of genetic decay is simply one more way God reminds us of the Fall (Genesis 3) and of our complete dependence upon Him.


Behe, M. J. (2010), “Experimental Evolution, Loss-of-Function Mutations, and ‘the First Rule of Adaptive Evolution,’” Quarterly Review of Biology, 85[4]:419-445.

Sanford, J.C. (2008), Genetic Entropy & the Mystery of the Genome (Waterloo, NY: FMS Publications).


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