The evolving world of epigenetics - 18 August 2012

Genomics Forum blogging team at the Edinburgh International Book Festival 2012
Blog by Chris Berry

Our understanding of life sciences has progressed apace during the last couple of decades.  From the development of mammalian cloning technology that brought us Dolly the Sheep, to the decoding of the human genome, we have made significant advances in genomics. This expansion of our knowledge has resulted in the development of new techniques that potentially could benefit humankind in a number of areas.  Yet just when we begin to think we might soon be masters of the genomic universe, a new kid on the (genetic) block has emerged, which may have considerable implications for both life sciences and society in general.

This relatively new science of epigenetics was the focus of a fascinating event – The Epigenetic Evolution – which took place at the Edinburgh International Book Festival on 18 August.  Featuring a panel comprising biological, medical and social scientists – and expertly chaired by Richard Holloway – it fell on the shoulders of Nessa Carey – leading industrial life scientist, and author of The Epigenetic Revolution – to explain to the capacity audience exactly what epigenetics entails.

The key clue, Nessa explained, is in the “epi” part of the phenomenon’s name, which is derived from the Greek for “on”, or “in addition to”, meaning that epigenetics refers to traits or expressions within organisms that cannot be explained simply as being derived from the genetic code.  There must be other factors acting in addition to the DNA.

At its most basic, the audience was informed, the influence of epigenetics can be recognised where the DNA of two organisms is identical, but the way in which they appear or behave is not.  For example, mice in a lab may be engineered to be genetically identical but they will have a range of body weights.  Even in familiar nature, epigenetics can be observed – a caterpillar and the butterfly it transforms into share identical DNA, but appear vastly different.  So if organisms have an identical genetic code, what causes such variability in its expression?

As the event panel set out, the old argument for this variability used to centre on the “nature versus nurture” proposition, basically identifying “the environment” – effectively an amorphous conglomeration of everything that isn’t genetic - as being the factor influencing the way seemingly identical genes are expressed.  Yet this explanation is deficient, insofar as there has to be a specific mechanism that, at any one time, influences exactly which genes in our genomes are turned on, turned off, and even how “loudly” they are expressed. 

The science of epigenetics has identified small chemical groups – most notably those called methyl groups – which don’t form part of an organism’s DNA, but rather attach “above” this, playing a key role in influencing how genes are expressed.  As Nessa Carrey summarised, it is these epigenetic markers that exist “on, in addition to, as well as” the genetic code, which are vital in switching certain genes on and off – “preventing teeth growing in our eyeballs, and allowing a caterpillar to transform itself to a butterfly…”

With the audience now familiar with the scientific basis of epigenetics, things became even more fascinating as consideration was given to the implications this might be having upon health and society.  For it transpires the epigenetic markers that play such an important role in how our DNA is interpreted can potentially be influenced by a range of environmental factors when – for example – a child is developing in the womb, when it is in its early life, and even, to some degree, when it becomes an adult.  And it is possible that someone’s epigenetic “fingerprint” can even be passed on to future generations.

The way in which social factors – such as deprivation – can impact human epigenetics, and then manifest itself in a population’s health, was elaborated on by Paul Shiels.  Based at Glasgow University, Paul is undertaking research into the links between accelerated ageing, disease and social deprivation, and focusing his studies on populations within Glasgow.  Paul identified that whilst some areas of Glasgow experienced some of the longest life expectancies found in Europe, other populations within the city had some of the shortest.  

His research has indicated that there were significantly lower levels of the epigenetic markers present in blood samples taken from individuals forming part of populations from the deprived areas of Glasgow, than those in the more affluent areas.  Levels of such epigenetic markers are primarily fixed in the womb, and naturally decline as a person ages, but it appears that factors such as the stress experienced by mothers living in deprivation whilst pregnant could result in much faster “epigenetic ageing” in their children.  Significantly, it is believed that this could have implications for the prevalence of high levels of poor health, resulting from cancer, heart disease etc., so frequently seen in deprived areas of Glasgow – the so-called “Glasgow effect”.

The considerable sociological implications of Paul Shiels’ medical research were highlighted by social scientist and Genomics Forum Director, Steve Yearley.  Steve pointed out that the apparent influence deprivation has upon epigenetic factors has major implications for politicians and those engaged in social policy, not only in Scotland but throughout the UK and globally.  This raised a swathe of potential issues.  Should social policy proactively focus on alleviating the deprivation-related factors that cause women to experience stress during pregnancy, in order to minimise premature epigenetic ageing in their children?  Could we develop ways to reverse the epigenetic impacts demonstrated by adults currently living in deprivation?  Ultimately, might it even be possible to produce epigenetic-based therapies to improve the overall health of deprived communities?

Most apparent, however, was the necessity for biological, medical and social scientists to work together to improve further the understanding of the links between epigenetic factors and how these are influenced by external players - such as deprivation and associated stress.  This could then ensure that resources dedicated to addressing deprivation and its consequences upon society are most effectively utilised.

The session concluded with an array of probing questions from the audience to the panel: 

Why might apparent epigenetic impacts possibly causing such comparatively high levels of ill-health in Glasgow?  Paul Shiels speculated that there might even be, as yet, undefined epigenetic co-factors from Glasgow’s industrial past that were amplifying those associated with deprivation.  

A woman who had conceived a child thanks to a Glasgow-based egg donor enquired about the epigenetic implications for her child.  Epigenetics can currently only really examine trends in population cohorts, as opposed to individuals, the panel concluded.

Could the high prevalence of Multiple Sclerosis (MS) in Scotland be down to epigenetic factors?  Nessa Carey indicated that certain traits of this disease might imply epigenetics could play a part, but significant further research was needed to identify this definitively.

And all too soon, a truly enthralling session concluded.  One that demonstrated exactly what such events at the Edinburgh International Book Festival can do so well:  take a seemingly complex concept; engage an audience by making this accessible; and then demonstrate the consequences such scientific developments might have for the audience’s own lives and wider society as a whole.