Epigenetics: Above and Beyond Genetic Determinism

Conscious choice and individual experience have a role to play in the progression of evolution and the emergence of new species. 

For those visual learners among you (or those of you who don’t want to read 3,000+ words), here’s a video that covers some of the concepts in this article. 

Where does consciousness fit into biology?  What defines a living thing?  How can we influence the evolution of the human race?  These are just a few of the deep and universal questions that the new science of ‘epigenetics’ may be able to answer.  In this article, I’ll give a brief explanation of epigenetics and how it relates to these questions.  But be aware that this is just a shallow overview — I recently published an entire book on the topic, and even that wasn’t enough to review many important elements of epigenetics.  Here’s an overview of what this article will cover:

I) On Top of Genetics

II) In Addition to Genetics

III) Above and Beyond Genetics

IV) A Bridge Between Darwin and Lamarck

V) The Influence of Choice and Experience

VI) Science, Epigenetics, and Consciousness

Whether it was through the human genome project, genetic ancestry testing, or genetically modified foods, everyone has heard of genetics.  But a much more interesting idea called “epigenetics” is just beginning to emerge in the collective awareness of humanity.  The prefix ‘epi’- is derived from Greek and has three distinct translations: on top of, in addition to, and beyond.  Because of these three meanings, there is quite a bit of controversy currently surrounding epi-genetics.  So, let’s briefly explore each of these definitions and what they might mean for science, evolution, and consciousness. 

I) On Top of Genetics

Gene expression is dynamically regulated through changes in chromatin structure and chemical modifications that physically sit on top of DNA. 

Figure 1: (from bottom to top) DNA base pairs (also known as nucleotides) come in four flavors: A, T, C, and G. These molecules interlock to create strands of DNA that then twist into a helix.  DNA helices get wrapped around proteins called histones, and the combination of DNA + protein creates a “beads on a string” structure called a nucleosome.  This beaded string of DNA and protein gets wrapped up even tighter into coils called chromatin, which are the basic building blocks of chromosomes. 

In its most scientifically-grounded sense, epigenetics refers to processes that physically occur on top of genetics.  Nearly every cell in your body contains a full copy of your genome, which is six and a half feet (~two meters) worth of DNA.  Because cells are approximately one million times smaller than this, DNA needs to be wrapped very tightly into bundles that most people know of as ‘chromosomes.’  The smallest chromosome in your body, Chromosome 21, contains over 40 million base pairs of DNA (the As, Ts, Cs, and Gs seen at the bottom of Figure 1), while the largest chromosome in your body, Chromosome 1, contains over 250 million base pairs.  These base pairs bind together to create individual strands of DNA, and these strands interlock into a zipper that twists into the classic DNA helix.  But any given double-stranded helix of DNA doesn’t just float freely throughout a cell.  Instead, these twisted strands of genetic material get wrapped around proteins known as histones, which creates structures called nucleosomes (see Figure 1).  This composition of DNA + protein gives an uncoiled chromosome the appearance of ‘beads on a string’ (see Figure 2).  This ‘beaded string’ of DNA is then packed tightly into coils called chromatin, which is the basic unit that composes a chromosome. 

Figure 2: DNA strands don’t float freely throughout the cell, because they get quickly degraded by nucleases (DNA-specific enzymes) which prevent viral and bacterial invasions.  Instead, DNA is wrapped around proteins called histones, which makes an unraveled chromosome resemble “beads on a string.”  The white arrowheads indicate naked strands of DNA and the black arrowheads indicate the points at which a DNA strand wraps around histones to create a nucleosome. 

Since our cells need to physically access DNA in order to use it, the shape of a chromosome can determine which genes get expressed.  Active gene expression requires loosely packed chromatin — if chromatin is wrapped up too tightly it physically obstructs the genes contained within its structure.  Therefore, chromatin provides our cells with a powerful genetic control mechanism, like an “on/off” switch for specific genes.  Unwinding the chromatin around a certain gene provides the opportunity for gene expression, while tightly winding the chromatin around a certain gene effectively silences the expression of that gene.  As easy as flicking a light-switch.  In this way, genes can be regulated over the long-term (years to months) or the short-term (days to hours).  In fact, this mechanism constantly changes the levels of gene expression in your body in a rhythmic fashion over the course of a day through a process known as ‘the circadian rhythm.’  And that is the first meaning of ‘epigenetics’ as on top of genetics: the dynamic regulation of gene expression through changes in chromatin structure and chemical modifications that physically sit on top of DNA. 

II) In Addition to Genetics

Entirely non-genetic mechanisms of inheritance operate in addition to the heredity of genetics. 

In a more controversial sense, epigenetics refers to things that are transferred from generation to generation in addition to DNA.  DNA has been considered the carrier of heredity since its structure was discovered in the 1950s.  Up until now, it has been assumed that biological inheritance is mediated by genes alone.  This prevailing view is referred to as neo-Darwinism, The Modern Synthesis of Biology, or the gene-centric view of evolution.  But, according to the theory of epigenetic (or non-genetic) inheritance, there are an untold number of heritable factors that cannot be explained solely by the replication of DNA from parent to child.  For example, the copying of behavioral patterns, like mimicry of other people’s actions; the transmission of cultural information, like the acquisition of language; the inheritance of environmental factors, like houses and cities; the heritability of microorganisms, like the transfer of vaginal flora during childbirth; and this list could go on and on. 

Figure 3: The word “epigenetic” was coined by C. H. Waddington in 1942, but the topic has only just started to gain popularity.  According to PubMed, the number of yearly references to the word “epigenetic” has drastically increased in the scientific literature since the year 2000. 

Epigenetics as non-genetic inheritance becomes particularly controversial when it is extended to psychological processes, because it means that our identities and memories may be influenced by the choices and experiences of our ancestors.  As you can see in Figure 3, the science is relatively new — epigenetics burst onto the scientific scene just around the turn of the new millennium.  Despite the recency of the field, some initial results suggest that non-genetic inheritance can be quite specific, such as liking the same foods as your parents, remembering the traumas of your grandparents, and even re-enacting the behavioral patterns of your great-grandparents.  These transgenerational effects seem to be mediated partly by the shape of our chromosomes on top of DNA, but the second meaning of epigenetics refers to the entirely non-genetic mechanisms of inheritance that operate in addition to the heredity of genetics. 

III) Above and Beyond Genetics

Conscious choice and subjective psychology have a role to play above and beyond genetics in the progression of evolution and the emergence of new species. 

Finally, and in its most controversial sense, epigenetics refers to the idea that conscious choice influences evolution at a level above and beyond genetic determinism.  This idea has been (somewhat derisively) named “Lamarckism” after the evolutionary theorist Jean Baptiste Lamarck, whose theories are often contrasted to Darwin’s.  Lamarck is best known for the theory of the inheritance of acquired characters, which modern day biology textbooks exemplify with a giraffe reaching into a tall tree to eat leaves (see Figure 4).  Lamarck claimed that as a giraffe repeatedly stretches into tall trees, the muscles in its neck will change over the course of its lifetime, and these changes can then be passed on to its children.  Eventually, over the course of thousands of generations, many small changes will add up to big changes and lead to the creation of a new species.  This process, now known as speciation, is a key component of the current conception of evolution. 

Figure 4: An image from a high school biology textbook depicting “Lamarck’s view” of evolution (which isn’t really an accurate description, because Darwin also held very similar views).  This image represents what would more accurately be described as the inheritance of acquired characters — the theory that experiences are biologically heritable. 

Modern-day biological education portrays Darwin as having fought and won a historical war of ideas — a war that Lamarck sorely lost.  Stephen Jay Gould, who was a very popular evolutionary biologist, described this phenomenon with the example of high school biology textbooks.  Here’s what he said about these textbooks: “…every single one — no exceptions — begins its chapter on evolution by first discussing Lamarck’s theory of the inheritance of acquired characters, and then by presenting Darwin’s theory of natural selection as a preferable alternative.”  Ironically, the theory of natural selection and the inheritance of acquired characters don’t contradict each other at all.  In fact, Darwin theorized that the inheritance of acquired characters was one of the mechanisms by which natural selection operated, in a process which he called “Pangenesis.”  Darwin hypothesized that each part of the body continually produced microscopic particles called “gemmules” that were responsive to the experiences of an organism.  In Darwin’s theory, these gemmules would circulate in the blood and collect in the gonads.  The gemmules that aggregated in the gonads could then be passed on to an organism’s offspring and provide those offspring with the traits and acquired characters of its parents.  So gemmules were essentially Darwin’s overextended conception of genes, which we now know to be carried by DNA and inherited through meiosis (also known as sexual reproduction).  But both Darwin and Lamarck might deserve more credit for these ideas than they are often given. 

“If I could choose, I would ban discussion of ‘the inheritance of acquired characters’…” — Dr. David Haig

The inheritance of acquired characters has been disputed for nearly 200 years, but the mounting evidence of epigenetic inheritance threatens to revive it.  It is no longer so far-fetched to think that our experiences can affect the lives of our descendants.  This idea is controversial to many scientists because it threatens to upset the commonly held neo-Darwinian notion that genes are the sole substrate of heredity (see the following articles as just some examples of the variety of views on the topic: Ptashne; Penny; Laland).  Take for example a quote from Professor David Haig, an evolutionary biologist and geneticist at Harvard, who writes: “If I could choose, I would ban discussion of ‘the inheritance of acquired characters’…” But banning all discussion of the inheritance of acquired characters would strike Darwin’s work from the historical record just as it would Lamarck’s (for the sake of posterity, let it be known that I consider Darwin to have been a much better scientist than Lamarck). 

The inheritance of acquired characters was not Lamarck’s original idea, and he never claimed it as his own.  He did, however, point out a powerful implication of the inheritance of acquired characters: that, within this framework, behavior can play a defining role in the process of speciation.  This implication might explain why neo-Darwinists are so resistant to the inheritance of acquired characters, because a blind and purposeless evolution is one of the core tenets of neo-Darwinism.  But a deep and disturbing conclusion of Lamarckism is that natural selection is not an unguided process.  Instead, conscious choice and subjective psychology have a role to play above and beyond genetics in the progression of evolution and the emergence of new species. 

IV) A Bridge Between Darwin and Lamarck

Exosomes are quite a lot like Darwin’s idea of gemmules — they represent a straightforward mechanism through which the inheritance of acquired characters could operate, almost exactly as Darwin theorized. 

Both Lamarck and Darwin espoused some version of the idea that our experiences, behaviors, and choices can be inherited by our descendants.  In other words, what we do changes who we are, and who we are influences who (or what) our descendants might one day become.  Many skeptics consider this claim to be unscientific at its best and laughable at its worst (see Figure 5).  So, let’s explore one instance of epigenetic inheritance that helps to turn this seemingly mystical idea into a tangible, scientific theory. 

Figure 5: A comment reply on Reddit from a self-proclaimed geneticist in response to this video. “ Could you give me a mechanism for how that works?”  is a very common argument against epigenetic inheritance.  Despite a growing body of literature on the subject, geneticists (and seemingly anyone who self-identifies as neo-Darwinist) treat anything vaguely Lamarckian with ridicule. 

Results from the lab of Dr. Kerry Ressler at Harvard’s McLean Hospital provide one of my favorite examples of how conscious experience can be epigenetically inherited in surprisingly specific ways.  In an elegant experiment, Dr. Ressler’s lab trained mice to associate a specific scent with the fear of getting shocked.  In this case, the scent was acetophenone, which smells a bit like cherry blossoms and is used in many sweet-smelling foods.  This kind of Pavlovian fear conditioning conditioning methodology is quite common in studies of behavioral psychology and neuroscience, but Dr. Ressler and his lab took their experiment several steps further than usual.  They bred the mice that had been fear conditioned and then studied the subsequent generations of mice.  They found that when a male mouse was conditioned to fear the smell of acetophenone, its children, grandchildren, and great-grandchildren became more sensitive to that specific odor (see Figure 6).  When compared to unrelated mice, the offspring of the fear-conditioned mouse showed a more intense reaction to acetophenone and could more easily detect small amounts of the odor for up to three generations. 

Figure 6: A graphical depiction of an experimental workflow by Kerry Ressler and Brian Diaz.  This image shows, from top to bottom, a mouse in the first generation (F0) being trained to associate an odor with an aversive stimulus.  This seems to cause epigenetic changes on specific genes in sperm cells of that mouse, which induce changes in the behavior of the two subsequent generations (F1 and F2) of mice. 

The specificity of this kind of transgenerational memory has not yet been found in humans, but it is startling to imagine an equivalent scenario in our lives.  For me, the smell of Febreze fabric cleaner brings back terrible memories — does this mean that my great-grandchildren will be more sensitive to the smell of Febreze?  Or that my negative associations with the odor of Febreze are related to the experiences of my ancestors?  As I write this, these questions do not have satisfying answers.  But Dr. Ressler’s results provide a tantalizing link between the heritable experiences of mice above and beyond genetics and the first meaning of epigenetics as on top of genetics.  Specifically, he found that the acetophenone-responsive neurons in the mouse’s nose showed a change in certain epigenetic modifications on top of one particular gene (Olfr151).  Amazingly, Dr. Ressler and his lab discovered that this same epigenetic changes occurred not only in the mouse’s neurons, but in its sperm cells as well.  It has not been rigorously established how neurons in the nose of a mouse can transmit information about sensory experiences to sperm cells in the mouse’s gonads, but these are very exciting and surprising findings. 

The mechanisms underlying transgenerational epigenetic inheritance haven’t been worked out in detail, but Darwin might have been eerily prescient with his theory of Pangenesis and the transmission of blood-born gemmules.  New evidence shows that our cells can produce tiny vesicles called exosomes that are filled with genetic material (and other kinds of information-carrying molecules).  These exosomes can be transferred from cell to cell across long distances and their contents seem to be responsive to the experiences of an organism.  In these ways, exosomes are quite a lot like Darwin’s idea of gemmules — they represent a straightforward mechanism through which the inheritance of acquired characters could operate, almost exactly as Darwin theorized.  And let’s not forget that these discoveries validate Lamarck’s theories as well. 

V) The Influence of Choice and Experience

Although the extent of epigenetic inheritance has yet to be explored, it is clear that our choices and experiences have profound effects that extend beyond our immediate conscious awareness. 

A lot of these ideas are speculative, because the science is quite new and most of it has been performed in non-human organisms.  However, there are examples of transgenerational epigenetic effects in people, like studies showing that the grandchildren of men who lived through a famine are more prone to obesity and that Holocaust survivors seem to pass on traumatic memories to their descendants.  While these examples are quite depressing, animal model studies are showing that positivity and good health also seem to be epigenetically heritable.  For example, a rat will become a more nurturing parent and more resilient to stress if its mother provided nurturing attention during development through licking, grooming, and physical touch.  And the specific epigenetic mechanisms that cause these effects are straightforward enough that a change in diet can induce similar effects.  It is being shown that diverse health problems like inflammation, cancer, and aging can be improved by modifying the epigenetics on top of our DNA through changes in lifestyle and diet (but please don’t try to treat cancer with a change in diet). 

Although the extent of epigenetic inheritance has yet to be explored, it is clear that our choices and experiences have profound effects that extend beyond our immediate conscious awareness.  Perhaps the mindfulness meditation I’ve been practicing has been altering my epigenetics on top of my DNA, and it is all but certain that your exercise routine affects genetic expression throughout your body.  So, the next time you have the opportunity to make a choice (Do I work out today?  Should I eat this sugary muffin?  Can I take the time to meditate?),  take a moment to reflect — your choices may be affecting unrealized lives in addition to your own life.  And there is the possibility that the sum total of your life’s choices will influence the evolution of our species far above and beyond your life and the lives of your immediate descendants.  Our personal influence on the overall course of evolution may be infinitesimal, but, if we let it, epigenetics can revolutionize the way we think about our biology, our relationship with nature, and our capacity to choose our own destinies. 

VI) Science, Epigenetics, and Consciousness

Epigenetics connects the calculating objectivity of science with the intangible mystery of consciousness. 

In truth, epigenetics is not some sort of reality-warping idea.  Epigenetics has already produced novel experimental techniques and new possibilities for preventing and curing diseases, but it is unlikely that anything will drastically change as a result of new experiments in the field.  Like other areas of biology, epigenetics is nothing more than a slow and methodical elucidation of the magnificent processes that are constantly happening within us (and around us).  Despite its scientific normalcy, epigenetics is paradoxically poised to shift the paradigm about evolution.  David Penny, professor of theoretical biology at Massey University, illustrates the tension between epigenetics as mundane and groundbreaking when he writes, “I guess that I see epigenetics (including environmental epigenetics) as continuing to learn about inheritance, rather than anything fundamentally new and different?”  In many ways, David Penny is correct — epigenetics is just the latest iteration in a long lineage of ideas about inheritance.  But, when we consider epigenetics within the light of evolution, it can act as a framework that allows us to see ourselves in a new way. 

Specifically, epigenetics connects the calculating objectivity of science with the intangible mystery of consciousness.  In some ways this is unfortunate, because the interface between the known and the unknowable is a breeding ground for extreme skeptics on the one hand and snake-oil salesmen on the other.  Adam Rutherford, a geneticist and author, both displays and describes these phenomena (respectively) in his article “Beware the Pseudo-Gene Genies.”  In his words, “The legion purveyors of flapdoodle love a real but tricksy scientific concept that they can bolt their pernicious quackery on to… Epigenetics is a real and important part of biology, but due to predictable quackery, it is threatening to become the new quantum.”  Epigenetics certainly has been hijacked by unscientific mystics like Deepak Chopra and Bruce Lipton, but Adam Rutherford would be dismayed to discover the deep (and truly scientific) parallels between epigenetics and quantum mechanics. 

I’ll leave it to you to explore the fascinating connections between the two fields (see Jorgensen, 2011).  Suffice it to say that epigenetics can overcome the genetic determinism of the neo-Darwinian view of evolution, just as quantum mechanics overcame the physical determinism of the Newtonian view of the universe.  Both of these seemingly disparate sciences call into question the distinctness of subject and object, of organism and environment.  And, like quantum mechanics, epigenetics provides no easy answers to the questions that are uncovered when we examine our conscious existence through the lens of science.  Scientists are still grappling with the incongruity of how we subjectively perceive reality and the implications of a quantum mechanical universe — it seems likely that the equivalent controversy surrounding epigenetics will continue for the foreseeable future.  But I predict that epigenetics will someday dissolve the popular dichotomy between nature and nurture.  Maybe then we will be closer to explaining the relationship between consciousness and biology, but I wouldn’t suggest holding your breath.  In the meantime, I hope you enjoy the exploration of these concepts as much as I do.  Thanks for reading, and let me know what you think about these ideas.