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David Marsh > Articles > Epigenetics - Current and Past Progress

Epigenetics - Current and Past Progress

by David E Marsh

in Positive Health issue 231 - July 2016

(see original article at link below for more information)

http://www.positivehealth.com/article/dna-gene-expression/epigenetics-current-and-past-progress


Abstract

To understand current progress in epigenetics we need briefly to visit 5th century BCE Greek thought onwards to our own 19th century CE. Empedocles, Heraclitus, Democritus, Hippocrates and Aristotle among others all had various views on environmental determinism, well described by Rebecca Stott in her excellent book Darwin’s Ghosts: In search of the first evolutionists.[1, 2]


Historical Perspective

It is only within the last 120 years that the environment has taken a back place behind the genetic determinism of the Neo-Darwinism created by Weismann, his Primacy of the DNA theory and later 20th century Neo-Darwinist thought which remains the orthodox evolutionary model to this today. (And no doubt well beyond: although this old model is being challenged with ever growing understanding of epigenetics.[2]

Before this time, and for preceding millennia the nurturing and supportive qualities of the environment were considered crucial. In the 18th century, the work of Goethe, Rousseau and Lamarck stressed the important roles played by the environment in what was to become known as evolution, or ‘transformisme’ in 18th and 19th century France.

Two decisive events during the 19th century collectively denigrated the importance of the environment. These were Darwin’s (and others') ideas regarding natural selection (1859>) but particularly Weismann’s papers Isolation of the Germ Plasm Theory (1890s>) and The All Sufficiency of Natural Selection.[6]

For although Darwin had stated that within his theory of evolution by means of natural selection “there were two great engines” driving evolution, "natural selection" itself, and "conditions of existence", he wavered over which was the most important.

In chapter 5 of the Origin of Species he says "I am convinced that Natural Selection has been the most important, but not the exclusive, means of modification." Then..."But the fact of variations ...occurring much more frequently under domestication than under nature...lead to the conclusion that variability is generally related to the conditions of life to which each species has been exposed during successive generations."

But he also stated, in the last paragraph of chapter 6 (all 6 editions), that “of the two forces, conditions were the most important”. [2, 3]

This led to confusion, and to the fear that he might be seen as straying into the ways of discredited Lamarck, whose theories he had struggled so hard to distance himself from. It also made it easy for him to be misinterpreted: as indeed he was only a few years after his death, by the German evolutionary biologist August Weismann.



Weismann’s insistence on his “isolation of the germ plasm theory”, in which he argued that no influences from somatic cells could affect the germ plasm - which existed in complete isolation. This is something we now know to be incorrect. Sadly, Weismann was blind by the time he published this: his ‘isolation theory’ was purely hypothetical. But acceptance of it led to the Primacy of the DNA theory leading to the genetic determinism we have known throughout the previous century until today. It is extraordinary to look back on it now to see how it all came about. [6]


However, the conventional viewpoint is now being challenged by scientists following completion of the human genome map and the growing understanding of epigenetics: the science of how environmental factors such as chemistry, nutrition, substrate, and stress and emotions can have a direct effect on the genome, making the same genotype behave or express itself in variable ways. These can lead to generational change in shape, form, function and behaviour; a growing number of scientists consider these impact energies play a more important part in the evolutionary process than had previously been realized.

More recently over the last 200 years the argument has abounded amongst evolutionists around the environmental theories of Jean-Baptiste Lamarck and Charles Darwin,[5] the genetic determinism of August Weismann the creator of Neo-Darwinism, and more recently the adherents of epigenetics and environmental evolutionists. A loose definition of the term epigenetic used to be covered by the phrase ‘environmentally induced modification’ (EIM). Until the beginning of the last century it was generally accepted that changes in the environment could result in reproducible change in the shape, form, function or behaviour of life forms. Such change was not the fixed type as occurs with mutations, but reversible. It was not therefore considered important in evolutionary terms. However, since the human genome map was completed in the early 21st century, such reversible change is at last being considered important: this is now known as epigenetic change. Debate continues amongst geneticists around this controversial subject to this day.

Simon House says “epigenetics is more than a fascinating and fast burgeoning field of biological research: it is of vital consequence to the human race, as we have come into arguably the worst crises in new forms of disease the human race has encountered.[4,7] These include the ‘non-communicable’ diseases related to the metabolic syndrome. Obesity, diabetes, cardiovascular and mental health disorders are increasingly recognized as connected with epigenetic changes of early origin.”

House describes epigenetics as “the process of a gene being switched off (silenced), or conversely being switched on (activated) by removal of the methyl group. Such changes reversibly modify the development of the organism without changing the basic gene-sequence (Epi- indicates 'on' the gene). Although the change is reversible, it can be passed on to subsequent generations.

"Epigenetic change can affect a cell's genome (genetic material) any time in the lifecycle, though the earlier in life the more potential. Reproduction involves major epigenetic changes in the genome of the developing oocyte (fertilized egg) and the genome from the sperm on fertilization. These changes allow some fine-tuning of the new organism to parental environment yet can also give rise to problems. The grandmother is 'reading' the environment for her grandchild - and to a lesser extent the grandfather too.

"Research articles are coming out fast on the relevance of epigenetic settings to many disorders, including: autism, psychosis, schizophrenia, Alzheimer's disease and cancer; the process of aging; and trans-generational effects. Environmental factors shown to be changing settings include nutrition, medicines, toxins and metals. Surprisingly epigenetics studies in human vaccination against infectious diseases are not apparent. [4,7]

"The Human Genome Project completed in 2003 met with general surprise. Instead of the 150,000 genes expected, to account for wide human variation, there was a mere quarter the number. This highlighted epigenetics to explain the wide variation. A few pioneers, however, were not surprised, notably the authors of The Driving Force (1989) and Nutrition and Evolution (1995), Michael A. Crawford and David E. Marsh, who describe how evolution has been driven by nutrition, as powerfully as by any condition of existence. Contrary to the Neo-Darwinists they point out that Darwin himself, in On The Origin of Species, relates the theory of natural selection to 'the two great laws - Unity of Type and Conditions of Existence' (consistency of a species and environmental conditions). Of these two great laws, he declares (concluding Chapter 6): ‘… the law of the Conditions of Existence is the higher law; as it includes, through the inheritance of former variations and adaptations, that of Unity of Type’. Epigenetics is part of this law’."[7]

Interestingly Darwin himself had proposed a mechanism for environmentally induced change that he called pangenesis. This he published in his 1868 book The Variation of Plants and Animals under Domestication (1868). He maintained that all cells contain tiny granules he called gemmules, which register any environmental change. “They are collected from all parts of the system to constitute the sexual elements, and their development in the next generation forms the new being; but they are likewise capable of transmission in a dormant state to future generations and may then be developed”.[5]

This was inspired guesswork for although epigenetic change works with a different mechanism, it produces similar results. It took scientists another 140 years to work out precise mechanisms - collectively first published in Handbook of Epigenetics. (Elsevier 2011).[7] Inspired prophecy might be a better term seeing as genes had not been discovered in Darwin’s time.

Unfortunately Darwin was not that good at explaining himself. He had said in different parts of the Origin that ‘natural selection’ was the most important of the two mighty forces that he suggested were driving evolution - natural selection and conditions of existence - then in another place that ‘conditions of life’ were the most important.

Dwelling on his various utterances, it seems clear that what he meant - and he says this somewhere else, “natural selection comprises of two great forces driving the upward thrust of evolution; one ‘natural selection’ leading to ‘the survival of those species best-fitted to their environment" (later abbreviated to survival of the fittest by Herbert Spencer) and 2; “the conditions of life… meaning the total impact energies of the environment.” It is unfortunate that he contradicted himself, so making it easier for successors to twist or misinterpret his message.

August Weismann
https://commons.wikimedia.org/wiki/File%3AAugustWeismann.jpg
By Linnean Society [Public domain], via Wikimedia Commons
This work is in the public domain in its country of origin and other countries 
and areas where the copyright term is the author's life plus 70 years or less.

Because he had not made himself entirely clear, after Darwin died in 1882, the creator of Neo-Darwinism, August Weismann from Freiburg University in Germany, argued in his paper The All-Sufficiency of Natural Selection that Darwin’s considerations of the environment - Darwin’s Conditions - were not necessary, as natural selection was “a force sufficient unto itself”. This he argued so convincingly all over Europe - including his lectures in Oxford, Cambridge and London – that for over a century scientists, medics, philosophers etc. fell hook line and sinker for his inexactitudes.[6]

Weismann should have called his theory Weismannism, rather than Neo-Darwinism, for he literally tore Darwin’s original thesis in half, cutting out that which is arguably the most important part - the environmental driving force which produced those species ‘best-fitted’ to their environment enabling them to become, often over countless generations, the dominant species in their epoch of evolution - or in the not entirely precise terminology of Herbert Spencer, ‘the fittest’.[6] Specialists regularly repeat this today, often calling themselves Darwinian - when they are neo-Darwinian or rather Weismannian.

Because of Weismann’s blindness, generations of our top brains have failed to realize the real power of the environment in almost every sphere of our lives. It explains how we do not appreciate or value the environment; why we do not understand the importance of, nor appreciate the quality of the foods we eat; the quality of the soils on which our food is grown… the quality of water in our streams, lakes, rivers and oceans, or the quality of the air we breathe… etc., etc. & etc.

Let us now jump to the current debate being played out on the world stage, by looking at Bill Sardi’s suggestion - Let’s Let Charles Darwin Sort-Out A Modern Debate In Biology describing the US federal project that involved 440 scientists from 32 laboratories from around the world, a project known as ENCODE (Encyclopedia Of DNA Elements). This concluded that 80% of the library of human genes (known as the human genome) is biologically functional. The results of ENCODE reported in September 2012. Strong criticism of its “extremely loose definition of ‘biologically functional’ soon followed.” [8]

ENCODE stunned the world of human genetics at that time as it was believed that only a small fraction (~3%) of genes actually produce proteins.

Sardi reports a further scientific reversal, 22-months later; scientists at Oxford University claim only 8.2% of our DNA is biologically active. Oxford researchers say the rest of the genome is leftover evolutionary material that has undergone mutational losses or gains in the DNA code.[9] Moreover, these researchers claim only a little more than 1% of human DNA accounts for the proteins that carry out most biological processes in the body.

Sardi suggests this is seemingly good news, describing how the human genome is comprised of about 21,000 genes, meaning only a couple hundred genes need to be influenced to produce a beneficial effect. Researchers he suggests have found that “only 295 genes are robustly associated with human aging.[10] There are natural or synthetic molecules known to activate or deactivate hundreds of genes at a time.[11] This suggests an anti-aging pill is within reach.”

Sardi goes on to describe how non-functional or “junk DNA” develops from DNA mutations. Over time mutations arise in DNA. Mutations occur on the DNA ladder. The steps of the DNA ladder called nucleotides (adenine, guanine, cytosine, thymine) may be substituted or be out of sequence, producing a mutation.[12]


Various studies estimate humans sustain 2.1-10.0 deleterious mutations per generation. This suggests, over time, that 90% of the human genome has mutated and is non-functional, as the Oxford University scientists claim.[13]. Oxford University researchers say these mutations have rendered most of the human library of genes, a copy which is stored in the nucleus of every living cell in the human body, as non-functional.


But let’s not overlook a convincing experiment where a segment of so-called junk DNA was deleted from laboratory mice. These animals experienced increased weight gain and mortality on a high-fat diet.[14]

Genetic versus Epigenetic

Inherited gene mutations represent only about 2% of all human disease.[15] Inherited diseases involve changes in the steps (nucleotides) of the DNA ladder. Gene mutations involves DNA structure.

However, genes are not static. Genes can make proteins, a process called gene expression (gene is switched ‘on’) or gene silencing (gene is switched ‘off’). Modifications in protein-making of genes that occur without changes in DNA sequence is called epigenetics. Most chronic disease is now believed to be epigenetic, that is, derived from gene protein making.[16]

Sardi suggests that “In between the lines of print readers find the scientific community is attempting to make the science fit an evolutionary model that makes little or no sense." (italics: DM)

The Oxford University scientists write that most of the human genome has been 'purified' by a theoretical biological mechanism called natural selection. (italics: DM) The unfit genes become mutated and the fit genes remain intact. The largest part of the genome “can be deleted without impacting fitness” of the species, they say.

Genetic Purification Questioned

The proposed idea of genetic purification by natural selection is on very shaky ground. As researchers at the University of Washington note, mutations rarely turn out to be beneficial.[17]

Another long unexplained phenomenon is that the genome size of the most advanced species, Homo sapiens, is 40 times smaller than a lungfish. An onion has a genome that is 5 times larger than a human.[18] One would think greater complexity would require more genes, not less.”[19]

Nature Versus Nurture

The behind-the-scenes battle going on is whether evolutionary forces are at work (genetic mutations over a long time) or whether relatively rapid epigenetic changes control the functionality of genes. Can biological function be explained without the dogma of random natural selection?[20]

The debate here is nature versus nurture, inherited biological destiny versus environmentally/molecularly alterable biology. The evolutionists cannot tolerate a departure from the evolutionary model. Oxford University researchers say the 440 scientists who authored the $123 million ENCODE project are dead wrong! It just can’t be.

Yet we know that most human disease is not inherited and involves ageing, which can be slowed or even reversed via epigenetics.

The epigenome is not only ‘imprinted’ in early human development but can be altered molecularly later in life.”[21]


Let Charles Darwin Sort it Out

Bill Sardi continues "With arguments for mutational/random natural selection/ evolutionary biology on the one hand and epigenetic/ environmental/alterable epigenetics on the other, it may be time to let the words of Charles Darwin sort out this argument.

"David Marsh of the McCarrison Society For Nutrition & Health in London, UK notes that Darwin spent a great deal of his time on his trips around the Galapagos Islands searching for possible mechanisms which communicate information from the environment to the human body. Darwin’s eloquent drawings showing changes in bird beaks over a short period of time (not millions of years as evolutionists claim) strongly points to environmental factors rather than inborn inherited factors that drive biological adaptation.

"Marsh notes that 'in each of his (Darwin’s) six editions of the Origin Of Species he stated there were two forces in evolution - ‘natural selection’ and ‘conditions of existence’; Darwin claimed the latter is more powerful', says Marsh. Marsh points out that natural selection has weak predictive power because of its dependence upon random events. Marsh says recent changes in human height and shape over the past century strongly point to Darwin’s 'conditions of existence'.[22] The same goes for the modern epidemic of diabetes.

Discover Magazine said it in 2006: 'DNA is not our biological destiny'.[23] In 2010 Time Magazine’s headline cover story said: 'Why DNA Isn’t Your Destiny'.[24]

"Epigenetics explains more about our biological destiny than evolution. Humans don’t need to be resigned to thinking the diseases that plagued their forefathers will inevitably affect them. Even existing diseases can be reversed mid-course. There is a lot researchers in biology aren’t telling you about epigenetics."[25]

It seems apposite to allow Charles Darwin the last word, by looking at his comments on chance…

"I have sometimes spoken as if variations were due to chance. This of course is a wholly incorrect expression, but it serves to acknowledge plainly our ignorance of the cause of each particular variation."[26]

Poor Darwin, arguably the greatest environmentalist ever, must be turning in his grave if he could only see what Weismann and many others since, have done to his beloved powerfully environmental theory.

References

1. Stott R. Darwin’s Ghosts: In search of the first evolutionists. Bloomsbury, UK. ISBN 978_1_4088_0908_2. 2012.

2. Crawford MA, Marsh DE. Nutrition and Evolution, Keats New Canaan, CT. USA. ISBN 06840_0876. 1995.

3. Darwin CR. On the Origin of Species by means of Natural Selection: or the Preservation of Favoured Races in the Struggle for Life. John Murray. London. 1868.

4. House SH. McCarrison Society for Nutrition and Health newsletter 43/1: Spring 2009.

5. Darwin CR. The Variation of Plants and Animals under Domestication’ (1868). John Murray. London. 1868.

6. Weismann A. Translation: Germ-Plasm, a theory of Heredity Charles Scribner's Sons – Full online text 1893. Also in Reference 2.

Weismann A. The All Sufficiency of natural selection. In Contemporary Review, 64:309-38; 596-610. 1893.

7. House SH SH House. Handbook of Epigenetics: The New Molecular and Medical Genetics. Editor: Trygve Tollefsbol, Publisher: Academic Press; 1st edition. Evolutionary Epigenetics. Chapter 26 - Epigenetics in Adaptive Evolution and Development: The interplay between evolving species and epigenetic mechanisms. ISBN-10: 0123757096, ISBN-13: 978-0123757098. 21 Oct 2010. House SH. Refs pp1-3

Golubovsky M, Manton KG. A three-generation approach in biodemography is based on the developmental profiles and the epigenetics of female gametes. Frontiers in Bioscience 10, 187-191. (2005).

Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L, Jia P, Assadzadeh A,Flanagan J, Schumacher A, Wang SC, Petronis A. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 82(3): 696-711. (2008)

Gillman MW, Barker D, Bier D, Cagampang F, Challis J, Fall C, Godfrey K, Gluckman P, Hanson M, Kuh D, Nathanielsz P, Nestel P, Thornburg KL. Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD). Pediatr Res. 61(5 Pt 1):625-9. (2007)

Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M, Golding J; ALSPAC Study Team. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 14.2:159-66. 2006.

Marsh DE. (2007) The Origins of Diversity. Nutrition and Health 19, No 1-2. 2007.

8. Proceedings National Academy Sciences April 2, 2013; Time Magazine Sept 6, 2012.

9. Science Daily July 24, 2014; PLoS Genetics July 24, 2014.

10. Aging Cell Oct 2011 onlinelibrary.wiley.com › ... › Cell Biology › Aging Cell

11. Current Drug Targets Dec 2011 www.google.co.uk/webhp?sourceid=chrome-instant&ion=1&espv=2&ie=UTF-8#q=+Current+Drug+Targets+Dec+2011

12. Genetics Generation. www.google.co.uk/webhp?sourceid=chrome-instant&ion=1&espv=2&ie=UTF-8#q=genetics%20generation

13. PLoS Genetics May 2014 www.plosgenetics.org/article/browse/issue/info%3Adoi%2F10.1371%2Fissue.pgen.v10.i05

14. Clinical Chemistry July 16, 2010; Nature March 18, 2010 www.lewrockwell.com/2014/07/bill-sardi/the-human-dna-debate/

15. Knowledge of Health April 25, 2014 https://mailman.stanford.edu/pipermail/protege-user/2014-April/000373.html

16. The Journals Of Gerontology: Series A: Biological Sciences & Medical Sciences www.researchgate.net/journal/1079-5006_The_Journals_of_Gerontology_Series_A_Biological_Sciences_and_Medical_Sciences June 2014.

17. PLoS Genetics May 8, 2014 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351

18. Genomicron April 25, 2007 www.genomicron.evolverzone.com/2007/04/onion-test/

19. see16. PLoS Genetics May 8, 2014.

20. Genome Biology & Evolution 2013. http://gbe.oxfordjournals.org/content/by/year

21. Seminars Nephrology July 2013. www.seminarsinnephrology.org/issues

22. Nutrition & Health Jan 2012. http://nah.sagepub.com/content/19/1-2/103.abstract

23 Discover Nov 22, 2006 http://discovermagazine.com/2006/nov/cover

24. Time Magazine Jan 6, 2010 http://content.time.com/time/covers/0,16641,20100118,00.html

25. LewRockwell.com April 25, 2014. 24. The Best of Bill Sardi. July 29, 2014. www.lewrockwell.com/2014/07/bill-sardi/the-human-dna-debate/

26. Darwin, CR. Origin of Species. Chapter 5. See References 3 and 2, Nutrition and Evolution, p112.