August 31, 2018, by Brigitte Nerlich
Epigenetics: Grappling with definitions
Definitions of epigenetics are notoriously slippery. This does not seem to hamper basic research. But it might hamper public understanding.
The words ‘epigenetics’ and ‘epigenetic’ have undergone quite substantial changes in meaning over time, leading up to a meaning which is now popular but open to misinterpretation. This history and increasing confusion has been charted, for example, by Haig, Deichmann, Greally, Henikoff and Greally, Deans and Maggert and many more.
But what do we mean by public understanding of epigenetics? We refer here not only to how people in the street might understand the word and concept (most people have, however, never heard the word before), but also academic ‘publics’, including medical doctors, philosophers, sociologists (of science), policy analysts, advertisers etc., indeed anybody not actively carrying out research in epigenetics… How is this public understanding shaped and on what conceptions of epigenetics, or indeed misconceptions of epigenetics, is it built?
In this blog post we, that is Aleksandra Stelmach and I, will only be able to dip our toes into this topic, which will be tackled in more detail in an academic article in the future.
Epigenetics on Twitter
While we were thinking about issues around meanings and definitions of epigenetics in academia and elsewhere, we came across an exchange on Twitter which can be seen as a sort of microcosm of debates about definitions of epigenetics (mainly amongst academic twitterati) that might provide some insights into understandings, misunderstandings and attempts at understanding through the use of metaphors and analogies.
It all started with a tweet posted on 27 August 2018 by Christina Farr (Reporter at @CNBC.com with a focus on health and tech) asking: “anyone have a super simple explanation of what ‘epigenetics’ is? I’ve been paying with a few ideas, but I think you guys can do better. Shoot…” And people shot! There were around fifty replies.
One reply/thread was by John Greally who is very active on twitter dispelling myths and misconceptions about epigenetics.
His thread recounts the history of definitions of epigenetics, from a developmental to a molecular one, leading up to the most recent but most misleading one: … “(5) Then the era of genomic biochemistry exploded, and a lot of regulators of the genome started to become discovered. Needing a name for this, the biochemists back-translated #epigenetics to epi-above/upon-genetics DNA sequence.” “(6) This definition covers every single genomic regulator, as we’ve thrown out the requirement that processes be heritable through cell division. The one regulator we don’t include, oddly, as it probably drives most #epigenetic processes, is transcription factors”.
We won’t go into the scientific intricacies of this explanation (comments welcome though, especially from biochemists), but we want to stress that this back-translation is very popular in academia, and we have employed it ourselves.
It is also used in the Wikipedia article on epigenetics, which, a few days later, provoked some debate, with John Greally remarking: “The wikipedia definition is based on the genomic biochemists’ epi+genetics travesty of a back-translation, with a tincture of heritability, a tip of the hat to cell differentiation, no wonder people are confused.” The wiki article itself would also deserve some analysis in the future! But back to Greally’s thread in answer to Christina Farr’s question.
As people had already begun to supply definitions, he warned her that “(8) The responses you’re getting to your question are focused on the epi+genetics definition. We can’t do simple let alone super-simple for you, when the term #epigenetics is ambiguous even for people working the field. To claim otherwise is misleading.” He put it more forcefully in 2016 when he said: “The shift in use of #epigenetics from developmental to molecular biology completely screwed the definition”.
Apart from the long thread supplied by Greally, what are the other answers to Christina Farr’s questions about a simple definition of epigenetics? The responses can be roughly grouped into three (as far as we can judge): those staying within mainstream of epigenetic science, those straying beyond mainstream epigenetic science, and those providing metaphors and analogies.
Venturing beyond mainstream science
The first tweet we saw just said: “Lamarckian theory updated”. This view of epigenetics is widespread in some parts of academia, especially ‘bio-adjacent fields’, including the philosophy and sociology of science/biology, influenced in part by scientists like Jablonka, Laland, and Szyf, for example. Most recently, Peter Ward, a paleontologist, has written a book based on this hypothesis entitled Lamarck’s Revenge.
Genes and genomes
This nod to Lamarckism is often linked to a rejection of some central tenets of mainstream genetics and genomics, especially a view attributed to classical genomics, namely that genes/genomes are fixed and rigid entities. It is then claimed that after the advent of epigenetics, we can finally see them what they are, namely flexible, reactive and dynamic entities. As one tweeter writes: “How your so-called unchangeable genes can change? The answer is epigenetics”.
Nature and nurture
Szyf is mentioned in a response that focuses on nature and nurture, also a strong talking point in sociological research into epigenetics. “Nurture impacts nature: life events alter your DNA, and you pass these changes along from generation to generation. See TED talk by Dr. Moshe Szyf”.
Transgenerational epigenetic inheritance
Transgenerational epigenetic inheritance is a recurrent topic in sociological writing, and also in biological writings that influence it. Here we find, for example, speculations about how social experiences can be passed down generations of humans, a hypothesis that is widely criticised by working scientists, such as Kevin Mitchell and Jerry Coyne for example.
One tweeter writes: “An organism’s environment can have an effect on what genes are expressed, and those changes can be passed down to later generations!” The next tweet goes even further! “On a slightly different direction, I think some of the deep emotions we experience are actually epigenetic memories from emotions experienced by our ancestors”…..And this one goes further still: “Epigenetics from ancient Indian spiritual tradition: Every thought, word, and action leaves an imprint on our DNA- that can be manifested in our life or future family’s life”….
As PZ Myers said in a blog post from 2015, epigenetics deals with “mechanisms that modify the expression of a genetic signal”. Gaining insight into these mechanisms is essential for understanding life, development and disease, from cells upwards. This is also important in evolutionary terms, as “gene expression is constantly being tweaked and modified” prompted by environmental triggers. But this does not mean, he stresses, that “you can explain a complex, higher-level psychological phenomenon like resentment of your mother” by reducing it to “a chemical reaction”!
And so we come to more mainstream science definitions (as far as we can tell).
Staying within mainstream science
One tweeter rehearses one of the most wide-spread definitions: “Epigenetics describes how gene expression changes occur without changes to the DNA sequence.” Another points out: “Post-translational modifications that direct gene expression. But since the modifications aren’t inheritable, it’s not really genetics.”
Others focus, rightly, on cells: “All of our cells have the same DNA – but epigenetics provides the next level of instructions to distinguish between a beating cell in the heart and a breathing cell in the lung.” And: “Genetics maintains information across an organism’s lineage. Epigenetics maintains information across a cell’s lineage.” And: “Cells in the body come from one fertilized egg. Epigenetics refers to the changes of gene expression of each cell as it specializes to function as part of a tissue. This is a fascinating journey for each cell & terrifying when the cell stops following the rules producing cancer!”
Another tweet focuses on the influence of the environment: “How environment impacts the expression of genetics. You can be ‘genetically pre-disposed’ to something but may never actually experience it unless the triggers are there. A example of this is Celiac Disease: a number of ppl have g-intolerance but don’t express signs for years.” Another points out: “Genes that ‘switch on’ based on environmental factors. For example, average coyote litter size increases when the local coyote population is under stress.” This brings us to metaphors and analogies…
Metaphors and analogies
Some of the metaphors and analogies used to define epigenetics are well-known and rooted in older ones, familiar from genetics and genomics, some are more creative.
Two tweets use computer metaphors: “Computer analogy – genome is hardware, epigenome is software (which can be changed)” and, the other way round: “Genetics is the software. Epigenetics is the user profile.”
Many definitions of epigenetics have been linked to the on/off switch metaphor (see Stelmach and Nerlich, 2015). One tweeter just said: “Turning genes on and off.” Whereupon another replied: “Specifically, it involves the factors that manipulate DNA’s 3D conformation / accessibility so that different genes can be turned on (expressed) or off (silenced).” Another tweet links the switch metaphor to the script metaphor: “Genes alone aren’t able to explain differences in genetic scripts. Something turns them on and off—epigenetics studies the driver’s of change”.
So we come to various book, script and language metaphors: “If genome is a recipe book and all cells have a copy, how does each cell know which recipes to use? Only skin cells need recipe to make pigment, for example. Epigenomics provides ‘post-it notes’ in the recipe book, so each cell only uses the right recipes”. “I always liked the idea that epigenetic marks (themselves only one aspect of epigenetics) are ‘annotations’ to the genome–they don’t change the text itself, but they affect how it’s interpreted. Maybe that’s too high-falutin’, but I find it clarifying.” “It’s like putting an accent on your words where genetics is changing the language.” “Hollywood analogy: DNA is the script (fixed) – epigenetics are the actors (variables that influence the end product)”.
Some tweeters homed in the ‘music of life’ metaphor. One wrote: “The musical score vs how you play it.” Another said, on a similar note: “genetics are the keys on the piano, epigenetics are the songs that are played”, and got the reply: “So is the piano the Proteome then?! :)”, and the first one retorted: “yes haha brilliant! and the pedals microbiome?!” expanding the metaphor into a little bit of absurdity perhaps!
There were however some tweeters who were more creative in their metaphor/analogy use: One defined epigenetics as: “Levers that affect gene expression. e.g., A tortilla, meat, salsa, avocado,…thrown on a plate do not become a delicious taco. Those things that can affect how the taco tastes (how meat is cooked, temperature, order & amount of ingredients,…) is epigenetics.” Others wrote: “Regulating genes without changing them. It’s like being a parent or a pet owner.” “How we are wired is the primer, the environment pulls the trigger and fate does the rest…..or something like that” and finally: “Bowling analogy: Genome sets up the pins, epigenetics tells you what knocks them down.”
There was also a tweet that engaged in wordplay: “Or: ‘It matters not only what genes you have but also how you wear them’”. Very nice!
What is epigenetics and who can define it?
As we have seen, many people threw definitions of epigenetics into the ring after Christina Farr asked her question, but what to make of these definitions? Can one classify them as we did? What about the metaphors and analogies? Do they illuminate or obscure? Comments welcome!
Some tweeters engaged with these questions and wrote: “These responses seriously make my head hurt. Not everything can or should be summed up by a catchy analogy. Some topics really aren’t all that simple…”. Another attached a picture of a quote by Haruki Murakami: “Some things in life are too complicated to explain in any language” – and in any metaphor?
There was also some reflection on who contributed definitions and metaphors. Somebody said in not too complimentary terms: “the chasm between what bio-adjacent people think (I am including a lot of MDs who are not doing research but ended up commenting about ‘epigenetics’ […]) and what is actually true is kind of amazing..”
The concept of ‘bio-adjacent people’ is intriguing and one should perhaps look at this more closely in the context of the emergence of bio-social research agendas based on various interpretations of epigenetics. This still leaves the question: is there a true definition of epigenetics?
The ‘truest’ one might be this one, provided in answer to Christina Farr’s question: “A very nascent (and often over-hyped) study of the ways a gene expresses an organism’s characteristics”.
It is important to monitor emerging and changing definitions, meanings and misconception of epigenetics that circulate in the public sphere, including academia, in order to see through what’s hype and what’s reality. This small analysis of a Twitter conversation provides some insights into what’s ‘out there’.