Lecture 9: Epigenetics

 Foundations of Liberty
The Intellectual Crisis of the Modern World

A Lecture Series with Prof. Thomas Patrick Burke

In the last lecture we suggested that modern genetics, though technically an immense advance on the biology of Darwin’s time, has repeated Darwin’s crucial philosophical error in regard to mechanistic and teleological causation. Darwin believed he explained evolution not as the work of any purpose, but as purely the product of chance, resulting from the accidental struggle of living beings for existence and the survival of the fittest. But he failed to notice that the struggle of living beings for existence is driven by a species of purpose: not the conscious purpose of a divine mind, indeed, at least so far as our experience is concerned, but natural purposes:  the desires all living things have to live, to grow according to a definite plan, to heal their wounds and to reproduce themselves. Natural purposes are genuinely purposive or teleological. They cannot be explained by mechanistic causation, we argued, because they reverse its causal order.  In mechanical causation the cause must exist before the effect, but in teleological causation it is the effect itself that is the cause.

What Darwin failed to notice, modern genetics, which assumes, as he did, that living beings are machines, has also failed to notice. For it does not recognize that there can be any such thing as a purpose anywhere. All talk of purposes, in its eyes, including the conscious purposes of human beings, is merely metaphorical, a figure of speech which is not to be taken literally. For machines cannot have purposes.

For our part, while we accept that science must, for practical reasons of prediction and proof, as well as the rational requirement of Ockham’s Razor, limit itself to mechanistic causation, we do not accept that the whole of reality is mechanistic, but we accept instead the universal testimony of human experience that purposes and the minds that produce them are real, including natural purposes. Scientific method is the arbiter of proof, but not of knowledge. There are at least four kinds of genuine knowledge that lie outside the realm of proof and therefore of science, though not of reasonable belief. Scientific method does not extend to the knowledge of unique individuals, of historical knowledge, of subjective experience or the knowledge of values.

Within science itself, however, in very recent years discoveries have been made that seem possibly to open a door in this very direction. We will discuss two of these: “epigenetics” in this lecture and “emergence” in the next.



Darwin was not the first scientist to offer a theory of how evolution takes place. In 1809 the French biologist Jean-Baptiste Lamarck  (1744-1829) in his book Philosophie Zoologique suggested the theory of the inheritance of acquired characteristics. An acquired characteristic is one that you are not born with, but have developed through your own action, for example your response to your environment, as you go through life, before you have children. If you learn to play the piano well while young, this increases the likelihood that your children will be born with a gift for playing the piano. We often seem to experience this effect: we see that talent sometimes runs in families, and we are not surprised to find children following in their parents’ footsteps. On the other hand we also see there are many cases where this does not happen. So the theory was not considered tremendously satisfactory. Darwin did not rule it out, at least as a partial and subordinate explanation. But his followers did. They have typically considered that Lamarck’s theory is opposed to Darwin’s, and that Darwin’s theory disproved Lamarck’s. We find this view still in recent literature, such as in Dawkins, who deals with Lamarck’s theory rather ferociously, as we shall see. Surprisingly, however, the new theory of epigenetics, which has quickly become established, can be considered a version of Lamarck’s theory.


“Epi” is Greek for above, over and above, on top of, in addition to, outside of, and similar meanings. Orthodox genetic theory has long taught that all transmission of traits from one generation to the next takes place exclusively by means of the sequence of “nucleotides” or “inheritance-molecules” in the genes. Epigenetics is something over and above genetics. It means the revolutionary discovery, which has been made only in the last decade or so, that pathways exist outside the genetic sequences by which traits can be handed on from one generation to the next. This discovery is, of course, scientific, it has taken place within the framework of science and by means of its techniques and conceptions, and so epigenetics in this sense is mechanistic. The pathways in question are mechanistic pathways. (Earlier, however, in the 18th century, the term “epigenesis” was used in philosophy without this restriction.)

In general, epigenetic events in the current sense prove to be the result of the fact we noted in an earlier lecture that although every gene in a living being is contained in every cell of that being, only some are activated or “expressed.” A cell of the liver contains not only the genes for the liver but also the genes of the lungs and other organs, but in the liver only the liver genes are expressed. In epigenetic effects the genes are not changed, but the expression of them is changed.The task of expressing the right genes rather than the wrong ones in a particular cell is carried out by enzymes. Epigenetics appears largely to have to do with the switching of genes on and off.

Since I am unfortunately not a scientist, but only a lover of science, perhaps the best way I can explain this new discovery is by recounting a number of news reports about it. I will take them mainly from a website called Science Daily. You will find more than 200 reports of these discoveries published over the last 10 years. Here are six, reproduced verbatim. Each one includes a headline and a summary. New reports are now published almost every day.


  1. Early Life Experience Modifies Gene Vital to Normal Brain Function

ScienceDaily (Sep. 28, 2010) — Early life stress, such as an extreme lack of parental affection, has lasting effects on a gene important to normal brain processes and also tied to mental disorders, according to a new animal study in the Sept. 29 issue of The Journal of Neuroscience.

In the last decade, researchers have found evidence that experiences can alter the form and structure of DNA, an effect known as epigenetics. Because these changes affect genes, events early in life have the potential to make a lasting impact on behavior and health. Recent studies focused on cancer and obesity have already shown the power of epigenetics.

In a study led by Tie-Yuan Zhang, PhD, of McGillUniversity, researchers investigated whether these changes might apply to the activity of genes in brain regions that control neural function and mental health. The authors explored how differences in a mother’s attention affect the GAD1 gene, which controls the production of a chemical vital to brain cell communication called GABA. Research indicates that GABA helps to regulate emotion, and that people with schizophrenia may have GABA deficits.

 The authors studied the maternal behavior of rats specifically bred to be either extremely caring or rarely affectionate. They found when the baby rats that were seldom touched grew up, specific regions of the DNA that controls the GAD1 gene were obstructed, likely leading to smaller amounts of GABA. On the other hand, adult rats coddled in the extreme as pups showed increased GAD1 gene production.

“A critical feature for the effect on gene GAD1 is that the immediate influence of maternal care is limited to a short period following birth, but the resulting changes are long-lasting, even into adulthood,” Zhang said.

These findings suggest that the early life environment can drive molecular changes that affect brain function and might determine a child’s predisposition to mental illness.

“We already knew that maternal care determined the stress responses of an offspring through a similar process, but this is the first time maternal care has been shown to link, via epigenetics, with a key enzyme that causes a major human disorder,” said Jonathan Seckl, MD, PhD, of the University of Edinburgh, and an expert on the molecular process of hormones. 

  1.  Environment and Diet Leave Their Prints On the Heart

ScienceDaily (Nov. 29, 2011) — A University of Cambridge study, which set out to investigate DNA methylation in the human heart and the “missing link” between our lifestyle and our health, has now mapped the link in detail across the entire human genome.

The new data collected greatly benefits a field that is still in its scientific infancy and is a significant leap ahead of where the researchers were, even 18 months ago. Researcher Roger Foo explains: “By going wider and scanning the genome [all the genes] in greater detail this time — we now have a clear picture of the ‘fingerprint’ of the missing link, where and how epigenetics in heart failure may be changed and the parts of the genome where diet or environment or other external factors may affect outcomes.”

The study originally began investigating the differences in DNA methylation found in the human heart. Researchers compared data from a small number of people with end-stage cardiomyopathy who were undergoing heart transplantation, and the healthy hearts of age-matched victims of road traffic accidents.

The DNA that makes up our genes is made up of four “bases” or nucleotides — cytosine, guanine, adenine and thymine, often abbreviated to C, G, A and T. DNA methylation is the addition of a methyl group (CH3) to cytosine.  When added to cytosine, the methyl group looks different and is recognised differently by proteins, altering how the gene is expressed i.e. turned on or off. DNA methylation is a crucial part of normal development, allowing different cells to become different tissues despite having the same genes. As well as happening during development, DNA methylation continues throughout our lives in a response to environmental and dietary changes which can lead to disease.

DNA methylation leaves indicators, or “marks,” on the genome and there is evidence that these “marks” are strongly influenced by external factors such as the environment and diet. The researchers have found that this process is different in diseased and normal hearts. Linking all these things together suggest this may be the “missing link” between environmental factors and heart failure.

The findings deepen our understanding of the genetic changes that can lead to heart disease and how these can be influenced by our diet and our environment. The findings can potentially open new ways of identifying, managing and treating heart disease.

As in most studies, as one question is resolved, another series of mysteries form in its place. The study shows that we are still on the frontier of epigenetics and only just beginning to understand the link between the life we lead and the body we have.

  1. Reawakening Neurons: Researchers Find an Epigenetic Culprit in Memory Decline

ScienceDaily (Feb. 29, 2012) — In a mouse model of Alzheimer’s disease, memory problems stem from an overactive enzyme that shuts off genes related to neuron communication, a new study says.

When researchers genetically blocked the enzyme, called HDAC2, they ‘reawakened’ some of the neurons and restored the animals’ cognitive function. The results, published February 29, 2012, in the journal Nature, suggest that drugs that inhibit this particular enzyme would make good treatments for some of the most devastating effects of the incurable neurodegenerative disease.

“It’s going to be very important to develop selective chemical inhibitors against HDAC2,” says Howard Hughes Medical Institute investigator Li-Huei Tsai, whose team at the Massachusetts Institute of Technology performed the experiments. “If we could delay the cognitive decline by a certain period of time, even six months or a year, that would be very significant.”

In every cell, DNA wraps itself around proteins called histones. Chemical groups such as methyl and acetyl can bind to histones and affect DNA expression. HDAC2 is a histone deacetylase, an enzyme that removes acetyl groups from the histone, effectively turning off nearby genes.

In 2007, Tsai’s group reported in Nature that this so-called epigenetic change can contribute to cognitive decline. They used a strain of mutant mice developed in her lab called CK-p25, which shows a profound loss of neurons and synapses, the junctions between neurons. The animals also carry the amyloid-beta plaques thought to cause Alzheimer’s disease and show impaired learning and memory. When Tsai’s team gave the mice drugs that block all HDACs, the animals sprouted more synapses and showed better memory function. There are 19 known HDACs.

  1. Saved By Junk DNA: Vital Role In The Evolution Of Human Genome

ScienceDaily (May 28, 2009) — Researchers at the Catholic University of Louvain and Harvard University show that stretches of DNA previously believed to be useless ‘junk’ DNA play a vital role in the evolution of our genome. They found that unstable pieces of junk DNA help tuning gene activity and enable organisms to quickly adapt to changes in their environments. The results will be published in the journal Science.

  1. Definition Of ‘Epigenetics’ Clarified

Science Daily (Apr. 1, 2009) — Ali Shilatifard, Ph.D., Investigator, has joined with a team of colleagues to propose an operational definition of “Epigenetics” — a rapidly growing research field that investigates heritable alterations in gene expression caused by mechanisms other than changes in DNA sequence.

The definition is intended to address confusion within the scientific community about the distinction between the mechanisms of epigenetic memory during early development versus those of dynamic chromatin regulation involved in differential expression of genes throughout adult life. The mechanisms underlying epigenetic memory are of great importance to human development and disease, but they are poorly understood.

The proposed definition reads: “an epigenetic trait is a stably inherited phenotype resulting from changes in a chromosome without alterations in the DNA sequence.” Shilatifard and colleagues have also proposed three categories of signals that operate in the establishment of a stably heritable epigenetic state. The first is a signal from the environment, the second is a responding signal in the cell that specifies the affected chromosomal location, and the third is a sustaining signal that perpetuates the chromatin change in subsequent generations.

“The field of ‘epigenetics’ has been an exciting one and has grown swiftly over the past several years, extending well beyond an initial discovery phase and identification of fundamental non-genetic and chromatin-based regulatory mechanisms,” said Dr. Shilatifard. “This collective effort to define and discuss ‘epigenetics’ is an attempt to add focus and clarity to this exciting and growing area of research.”

Dr. Shilatifard’s publication appeared April 1 in Genes and Development and resulted from a meeting on December 7-10, 2008 that he co-organized at Cold Spring Harbor Laboratory in New York to discuss aspects of epigenetic control in genomic function and to develop a consensus definition of “epigenetics” for consideration by the broader research community.

  1. Propensity for Longer Life Span Inherited Non-Genetically Over Generations, Study Shows

ScienceDaily (Oct. 20, 2011) — We know that our environment — what we eat, the toxic compounds we are exposed to — can positively or negatively impact our life span. But could it also affect the longevity of our descendants, who may live under very different conditions? Recent research from the Stanford University School of Medicine suggests this could be the case.

Blocking or modifying the expression of any of three key proteins in a laboratory roundworm increases the life span of not only the original animal, but also that animal’s descendants, the researchers found. This occurs even though the original modification is no longer present in the descendants. The finding is the first to show that longevity can be inherited in a non-genetic manner over several generations.

It’s tempting to translate the findings to humans, who share similar proteins with those studied in the worms in this work. While much more investigation is needed, the research at least hints at the possibility that modifications that occurred in your great-grandparents, perhaps as a result of diet or other environmental conditions, will affect your own life span.

“In some ways, this work relates to the idea of inheritance of acquired traits, which is almost heretical because it has long been discounted by the laws of Mendel,” said associate professor of genetics Anne Brunet, PhD. “But we show in this study that the transgenerational inheritance of longevity does occur in roundworms via modulations of proteins that normally add epigenetic modifications to chromatin.”

The term epigenetics describes a process by which organisms modulate their gene expression in response to environmental cues without changing the underlying sequence of their DNA. Chromatin, the tightly coiled complex of DNA and proteins called histones that keeps the genetic material firmly packed in the cells’ nucleus, can be modified in an epigenetic manner by addition or removal of chemical tags on histones or DNA itself.

Richard Dawkins Again

Perhaps from these reports it will be clear why I remarked that epigenetics is a version of the Larmarckian theory of the inheritance of acquired characteristics.  We will pause here to note that Richard Dawkins, in books published before these epigenetic discoveries were made, argued they were next to impossible. “It is not possible to prove that acquired characteristics are never inherited. For the same reason we can never prove that fairies do not exist. All we can say is that no sightings of fairies have ever been confirmed, and that such alleged photographs of them as have been produced are palpable fakes.” “Any categorical statement I make that fairies don’t exist is vulnerable to the possibility that, one day, I may see a gossamer-winged little person at the bottom of my garden. The status of the theory of acquired characteristics is similar.” (The Blind Watchmaker, 1986) In this, as in other important matters, he was mistaken.


We can see from our experience of living beings that they are not mere machines but are teleological or driven by natural purposes: all living things desire to survive, to grow and develop according to a definite plan, to heal their wounds and to reproduce themselves. It is reasonable, then, to see evolution as mainly the product of these natural purposes or desires. This does not rule natural selection out. But we should remember that natural selection is entirely a negative process: it destroys those species that cannot compete. The big question in evolution is: where or how does the spectacular improvement come from that we see in the kinds of beings that exist? Why are there not only the primitive organisms such as bacteria—many of which are extremely successful in reproducing themselves—but also plants? And given that there are plants, many of which we see are also astonishingly successful in the contest for survival, why are there also animals? And given that there are animals, which lead often very successful and flourishing lives, why are there human beings? Mechanistic causation has no way of itself whatever to create an improvement. If an improvement should happen to take place accidentally, it may or may not preserve it. It is not oriented towards the production or conservation of improvements. But we see that the natural purposes of all living beings are oriented towards improvement. The desire to live and survive the difficulties of life is always not only a desire to continue what already exists but also to exist in a better, more robust and effective way. The desire to grow and develop according to a definite plan is always a desire to overcome the difficulties that stand in the way of that. And the desire to reproduce oneself is similarly a desire to produce offspring that will be better able to survive and prosper. It is more reasonable and intelligent to view the human species as a result that emerges out of these natural purposes, rather than as a mere meaningless accident.

The importance of epigenetics is that it shows us in concrete detail how this goal may possibly be achieved.  Even though epigenetic effects can be negative as well as positive, destructive as well as beneficial, the fact that they exist shows us that the course of evolution is not autonomous, or governed by dynamics entirely from within, but can be affected by the external environment and interactions with other beings, as we would expect with living beings. It shows us that mechanisms are available to living beings by which they can adapt to the challenges of their environment and produce improvement.  It shows us mechanisms that teleologies can make use of to achieve their aims.

We see that adaptation is not restricted to the slow action of genes over many generations, but can take place rapidly. So long as inheritance was limited to the genes, improvement could take place only through accidental mutations of the genes. But most mutations are harmful to the organism rather than beneficial. Now we see that improvement can take place more creatively. Although the particular cases uncovered by science will necessarily be interpreted by it as mechanistic in character, they are mechanisms that can serve the creative natural purposes of living beings: survival, growth according to a definite plan, and reproduction.

Some Recent Books on epigenetics:

Nessa Carey, The Epigenetics Revolution, March 1, 2012 (reviewed in Wall Street Journal, Saturday, March 3, 2012)

Benedict Hallgrimsson, Epigenetics: Linking Genotype and Phenotype in Development and Evolution, 2011

Jeffrey M. Craig & Nicholas C. Wong, Epigenetics: a Reference Manual. 2011.

Trygve O. Tollefsbol, Handbook of Epigenetics, 2010