In his autobiography, Charles Darwin notes, “Towards the end of the work I gave my well abused hypothesis of Pangenesis. An unverified hypothesis is of little or no value”—the First-Wave of evolutionary thought. Today, Darwin’s sentiments on pangenesis have re-emerged, however, this time on genetics.

In this week’s edition of the journal Science published by the American Association for the Advancement of Science (AAAS), the focus is on epigenetics. An on-line issue even features a video by Science editor Guy Riddihough asking a number of top researchers a simple question: “What’s your definition of epigenetics?” And, “Their answers aren’t quite so simple,” according to Riddihough.

While Darwin’s theory of pangenesis in The Origin of Species gained little support, the emerging gene-centric model Second-Wave for evolution proposed by the giants of evolution starting with Theodosius Dobzhansky, Julian Huxley, Ernst Mayr, and Francis Crick, became the foundation of evolution of theory over the during the late twentieth century.

Crick named the theory, the “Central Dogma” of evolution. Evolutionary theory was envisioned as simply a process of genetic mutations acted on by natural selection.

Since then, the stage has been set to discover the anticipated Darwinian “slight, successive” sequence of genetic mutations associated with the evolution of new species. Not until just the last ten years has last the technological frontier been conquered, DNA sequencing, to validate the gene-centric theory of evolution.

Now with genetic evidence available to valid the Second-Wave, scientists are abandoning the gene-centric evolutionary theory for one big reason; there are no “slight, successive” genetic changes to validate the gene-centric theory of evolution as anticipated by neo-Darwinism, the Modern Synthesis, or the Modern Evolutionary Synthesis. From nature, the evidence is clear; any mechanism for evolution must exist beyond genetics—epigenetic.

Epigenetics major problem is, as Riddihough highlights, there is no consensus on what constitutes epigenetics, “Although epigenetics generally refers to the inheritance of variation above and beyond changes in DNA sequence, the term is becoming shorthand for a variety regulatory systems involving DNA methylation, histone modification, nucleosome location, or noncoding RNA.”

The once simple Second-Wave theory of mutations acted on by natural selection has now been given way to a Third-Wave of yet a vastly more complex theory, in yet some unknown system, and with yet some unknown mechanisms, as Riddihough highlights.

The Third-Wave of genetics, including epigenetics, has completely replaced the Second-Wave realm of theoretical evolution. Massimo Pigliucci in his new book entitled Evolution-The Extended Synthesis published by MIT Press, recognizes that the fundamental tenets of Modern Synthesis “are being challenged as either inaccurate or incomplete” and “all these molecular processes clearly demolish the alleged central dogma.”

To address the Second-Wave crisis and pave the way to the Third-Wave, Pigliucci and Gerd Muller in the summer of 2008 convened a workshop at the Konrad Lorenz Institute for Evolution and Cognition Research in Altenberg near Vienna, Austria. 

The workshop was entitled “Toward an Extended Evolutionary Synthesis?” Evolutionary academians from sixteen universities participated in the workshop. The workshop became known as the “Altenberg-16” and dubbed “The Woodstock of Evolution.”

Today, evolution is a philosophy looking for the evidence to support the theory. As such, the evolutionary industry has completed abandoned the Scientific Method.

Nature has spoken. Evolution, once a theory in crisis, is now in crisis without a theory.

In The Origin of Species, Charles Darwin uses the term information seven times. In all seven uses, information is only used in the context of gaining knowledge, “I have also reason to suspect, from information given me by Mr. W. W. Edwards, that with the English race horse the spinal stripe is much commoner in the foal than in the full-grown animal.”

Information is never used in the context of genetics. In fact, information is only used in the context of exchanging information between colleagues.  

“And it would appear from information given me by Mr. Watson, Dr. Asa Gray, and Mr. Wollaston… ”

“… as I have learnt from information and specimens sent to me by Mr. Salvin… ”

“Mr. Agassiz, to whose great kindness I am indebted for much information on the subject… ”

“This species is found in the southern parts of England, and its habits have been attended to by Mr. F. Smith, of the British Museum, to whom I am much indebted for information on this and other subjects.”

“Accordingly I wrote to Professor Miller of Cambridge, and this geometer has kindly read over the following statement, drawn up from his information.”

“… without any information in regard to their geological position, no one would have suspected that they had co-existed with sea-shells all still living.”

Little did Darwin know that even before the publication of the fourth edition of The Origin of Species in 1866, Gregor Mendel had presented the now-famous paper entitled “Experiments on Plant Hybridization,” laying the foundations of modern genetics.

By the mid-twentieth century, the study of evolution was focused on the gene centric information in DNA and RNA. Genetics is no small problem for Darwin. In a letter to Hugh Falconer in October 1862, Darwin wrote - 

I look at it as absolutely certain that very much in the Origin will be proved to be rubbish; but I expect and hope that the framework will stand.

The simple fact is, although, Darwin was certain his theory was “rubbish”, little did he expect that the framework would not stand, either. In the early twentieth century, following the rediscovery of Mendelian genetics Darwinism was replaced by neo-Darwinism.

Neo-Darwinism was further modified in the mid-twentieth century, replaced by the Modern Synthesis, also known as the Modern Evolutionary Synthesis. The basis of expanding evolution was based on the origin of new information through mutation plus natural selection—the Central Dogma of evolution. 

At the center of the controversy is information. In the biology textbook An Introduction to Biology, Gaylord Simpson, of the American Museum of Natural History, wrote -

Mutations are the ultimate raw materials for evolution.

But, how can mutations give rise to new information? Massimo Pigliucci and Gerd Muller, in their new book Evolution, the Extended Synthesis (2010) published by MIT recognize -

[F]or several years now dissenters from diverse fields of biology have been questioning aspects of the Modern Synthesis

The questioning centers on information. To the question, can functional information arise from mutations? Italian geneticist Giuseppe Sermonti replies -

Science has taken on the great wager … and lost.

 Darwin’s “framework” along with the unanticipated requiremenets for information has certainly not withstood the test of time. Evolution continues only as a philosophy—without a theory.

Charles Darwin lamented in his autobiography over ascribing to pangenesis in The Origin of Species - 

Towards the end of the work I gave my well abused hypothesis of Pangenesis. An unverified hypothesis is of little or no value.

While Darwin’s hypothetic pangenesis was an accepted theory in 1859, by 1864 French biologist, Louis Pasteur, had undermined pangenesis by demonstrating that life cannot arise spontaneously—life can only come from life. Darwin was right. Pangenesis is of “no value.”

By the mid-twentieth century, while Francis Crick and James D. Watson unveiled the molecular structure of DNA. In 1953, the momentum of evolution theory was rapidly defaulting to a mutation plus natural selection neo-Darwinian model, most commonly known as Modern Synthesis.

The gene became the center of Modern Synthesis theory and promoted as a “fact of life.” The fundamentals of Modern Synthesis gene-centric theory were declared by American geneticist Theodosius Dobzhansky

Mutations and chromosomal changes … constantly and unremittingly supply the raw materials for evolution.

By the early twenty-first century, however, the unifying theory of evolution began to unravel. In their 2002 book entitled Acquiring Genomes: A Theory of the Origins of Species, Lynn Margulis, and Dorion Sagan succinctly declare the now obvious fact –  

Mutation accumulation does not lead to new species or even to new organs or new tissues.

Giuseppe Sermonti, an Italian geneticist, in his 2005 book Why a Horse is Not a Fly notes that the late citadel of evolutionary theory, Modern Synthesis, was in fact a never event -

 To say that blind mutations are the driving principle of the world, and to rely on the rare fortunate mistake, is a poor resource, quite apart from the fact that transgressions of the kind needed by Darwinian evolution have never been documented.

In the new book, The Altenberg-16, An Exposé of the Evolution Industry, Suzan Mazur, explains the reasons for the emerging revolution in the evolution industry -  

[T]here is a need to challenge the prevailing Modern Synthesis because there is too much it doesn’t explain. For example, the Modern Synthesis was produced when genetics was still a baby and science has discovered all human genes there are to be found. We’ve only got 20,000 – 25,000 of them.

The number of genes, 25,000, is nearly the same number of genes in the fruit fly and in coral. Evolution from the simple to more complex is not supported by newly emerging scientific evidence in genetics.

Professor David Miller of the ARC Centre of Excellence in Coral Reef Studies and the ARC Special Research Centre for the Molecular Genetics of Development, notes - 

Corals are among the simplest animals in the world – yet they may possess a set of genes as large and complex as our own.

Twenty-five thousand is not only a numbers problem for the simple to complex evolution camp, 25,000 is a problem in cellular biology. How can just 25,000 genes alone control the function of millions of biological processes? Sermonti reflects on the dilemma –

It was thought that a gene count might offer a better index of organismal complexity…. And where did this all lead? To the conclusion, that biochemical complexity has little to offer in explaining evolution.

The gene-centric Modern Synthesis developed from an untested hypothesis. Once again, history has come full circle. Like Darwin’s pangenesis, the Modern Synthesis is in a game-changing crisis and theories of evolution are once again facing the “no value” charge.

The challenge facing the evolution industry is finding a theoretical successor—fast. History might repeat itself. Sadly, eight years after Pasteur undermined pangenesis Darwin in last edition of The Origin of Species in 1872, continued to promote the concept of pangenesis.

Evolution was a theory in crisis in the twentieth century, now evolution is in crisis without a theory. After 150 years, evolution, like pangenesis, continues as “an unverified hypothesis… of little or no value.”

The fruit fly is celebrating 100 years of research. Charles W. Woodworth at the University of California, Berkley, at the turn of the twentieth century, was the first to use the fruit fly as model in the study of genetics. Today, Drosophila melanogaster, the common fruit fly, has become one of the most studied organisms in biological research, particularly in the field of genetics.

In 1910 following Woodworth’s footsteps, at Columbia University from the top floor of Schermerhorn Hall, now known as the Fly Room, Thomas Hunt Morgan confirmed and extended Gregor Mendel’s basic principles of genetics. A year later, Morgan published his findings in Science, establishing the foundation for the emerging neo-Darwinism movement.

Morgan, in the book entitled The Mechanism of Mendelian Inheritance (1915) demonstrated how mutations using radiation on two-winged fruit flies resulted in four-winged fruit flies. The four-winged fruit fly was widely heralded as the earliest evidence that the first evolutionary step to produce a new species was a mutation.

The question, however, centered on whether the mutated four-winged fruit fly was a new species or an unsustainable aberrational freek. By 1963 after decades of research, the question could be answered definitively. Ernst Mayr, Charles Darwin’s twentieth century Bulldog, viewed the mutated four-winged fruit flies as “such evident freaks that these monsters can be designated only as ‘hopeless.’ They are so utterly unbalanced that they would not have the slightest chance of escaping elimination.” Mutation is not the gateway to evolution.

While mutations on the two-winged fruit fly served as a window to study theroretical evolutionary genetics for decades, mutations are now known not supply the raw materials for evolution. Italian geneticist Giueseppe Sermonti explains –

One spur to research on mutations was the hope that an accumulation of these might lead to a new species. But this never happened.

The fruit fly as a model for evolution via mutations gets even worse—there are no “slight, successive” genetic changes even between over 1,400 closely related Drosophila species.

The number of nucleotide base pairs Drosophila species ranges from 127 to 800 million. The probability of constructing a Tree of Life with “slight, successive” changes in nucleotide base pairs from species to species approaches the realm of impossible.

Each species of Drosophila appears to remain distinct and unique. The following table is the number of estimated genome sizes as measured by the number of nucleotide base pairs in several different Drosophila genomes.

Pierre-Paul Grassé, past-president of the French Academie des Sciences in the book entitked  Evolution of Living Organisms concludes – “The fruit fly [Drosophila melanogaster],the favorite pet insect of the geneticists, whose geographical, biotopical, urban, and rural genotypes are now known inside out, seems not to have changed since the remotest times”—evolution never happened. 

No wonder genetic researchers at Bioinformatics Research Center, North Carolina State University now bring into question whether genes even play a role in evolution between related Drosophila species. Wen-Ping Hsieh and collegues published in Genetics -

An emerging issue in evolutionary genetics is whether it is possible to use gene expression profiling to identify genes that are associated with morphological, physiological, or behavioral divergence between species and whether these genes have undergone positive selection. (1)

Genetic researchers from the Department of Ecology and Evolutionary Biology, University of Arizona, similarly discovered that “no strong evidence” in gene selection exists between Drosophila species and the respective proteins produced, “divergent expression”. Between Drosophila species, changes in genes do not correllate with changes in proteins. Jeffrey M. Good and collegues in an article published in Molecular Biology and Evolution, 2006, conclude -

Overall, we found no strong evidence for an increase in the incidence of positive selection on protein-coding regions in genes with divergent expression in Drosophila (2)

Genomic research looking for the “slight, successive” genetic changes required by neo-Darwinism is no friend of evolution. The survivors of 100 years of lab torture continue just as fruit flies.

The genome of D. melanogaster was sequenced in 2000. Most surprisingly, nearly 75% of known human disease genes are now known to have a recognizable match in the genetic code of fruit flies, and 50% of fly protein sequences have mammalian homologs. Mutations are either neutral or lead to disease—not evolution.

Today, over 100 years later, Drosophila serves as a genetic model for several human diseases including the neurodegenerative disorders Parkinson’s, Huntington’s, spinocerebellar ataxia and Alzheimer’s disease.

Reflecting on the limits of genetics in establishing the validity of evolution, Italian geneticist Giuseppe Sermonti weighs in –

Science has taken on the great wager … and lost.

1.  Wen-Ping Hsieh, Tzu-Ming Chu, Russell D. Wolfinger, and Greg Gibson. Mixed-Model Reanalysis of Primate Data Suggests Tissue and Species Biases in Oligonucleotide-Based Gene Expression Profiles. Genetics. 2003. 165: 747-757

2.  Jeffrey M. Good, Celine A. Hayden, and Travis J. Wheeler. Adaptive Protein Evolution and Regulatory Divergence in Drosophila. Molecular Biology and Evolution. 2006, 23(6):1101-1103

In 1943, published in a paper entitled “Mutations of Bacteria from Virus Sensitivity to Virus Resistance,” microbiologist Salvador Luria, biophysicist Max Delbrück, and bacteriologist and geneticist Alfred Hershey discovered that mutations occur at a constant rate. In 1969, they were awarded the Nobel Prize in Physiology and Medicine “for their discoveries concerning the replication mechanism and genetic structure of virus.”

The Luria-Delbrück Experiment opened the question, are mutations inherent to microbes for the purpose of adaption to rapidly changinging environments and not for evolution? While microbe resistance through mutation is a logical mechanism for evolution, the reality is the bacteria have remained a bacteria and the virus has remained a virus. Preexistent genetic variants determine the range of mutations. Pierre-Paul Grassé, president of the French Academy of Sciences, observed, “bacteria, the study of which has formed a great part of the foundation of genetics and molecular biology … stabilized a billion years ago.”

The question is whether the mutations are the “raw material for evolution” or nature’s means for the microbes to adapt to the environment. In a 2009 review article by entitled “Darwinian evolution in the light of genomics”, published in Nucleic Acid Research, Eugene V Koonin concluded, “There is no consistent tendency of evolution towards increased genomic complexity” through mutation as expected with current evolutionary theories. Mechanisms of evolution remain beyond any known natural law.

Reflecting on the role of mutations, Grassé questioned, “What is the use of their unceasing mutations if they do not change?” Grassé concludes, “the mutations of bacteria and viruses are merely hereditary fluctuations around a median position; a swing to the right, a swing to the left, but no final evolutionary effect.” Microbes undergo constant mutations, but do not evolve – mutation stasis.

*Nucleic Acids Res. 2009 March; 37(4): 1011–1034