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Should you switch on to epigenetics?

A field of scientific research is on the rise – one that makes powerful headline claims about how our life experiences can turn our genes on – and off – to shape the people we later become. The educational bandwagon is inevitable, writes Kat Arney, but do advocates of epigenetics have enough detailed evidence to persuade policymakers and pedagogues that this should be the next big schooling panacea?

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A field of scientific research is on the rise – one that makes powerful headline claims about how our life experiences can turn our genes on – and off – to shape the people we later become. The educational bandwagon is inevitable, writes Kat Arney, but do advocates of epigenetics have enough detailed evidence to persuade policymakers and pedagogues that this should be the next big schooling panacea?

It started, as so much in science seems to, with rats. Stressed-out baby rats, in this case: some with attentive mothers and some with mothers who were not so attentive. Those rats changed the way many scientists view nature and nurture. And those rats could eventually change the way you teach.

It was in 2004 when those rats ignited the study of epigenetics – a relatively new branch of science seeking to explain how the things that happen to us during a lifetime somehow imprint on our genes, affecting our bodies, brains and behaviour. They spawned numerous papers and multiple headlines.


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Eventually, the science leaked into the mainstream: epigenetic pancake recipes, epigenetic face cream, even epigenetic yoga are now presented to us as ways we can pimp our genomes by manipulating the activity of genes through food, cosmetics or activity to make us seem younger, healthier and smarter.

 

Inevitably, epigenetic concepts are also starting to drip through into the world of education. A new breed of biosocial scientist has arrived, using epigenetics to explain how changes in the environment can alter the body and brain, overriding genetic destiny and opening up new biological possibilities.

The ideas are exciting. But we must learn from the past – those instances when schools rushed to embrace theories that were subsequently debunked as pseudoscientific nonsense. Before the educational evangelists take hold of this emerging field of research and hold it aloft as the saviour of our children, we need to step back. Let’s look at this closely and critically, and make sure the science stands up to scrutiny.

Here comes the science bit

To put it simply, genetics is the study of what you’ve got written in your DNA, and epigenetics is about what your body does with it.

DNA is made up of four chemical building blocks, known as bases: adenine (A), cytosine (C), thymine (T) and guanine (G). The human genome contains about 3 billion of these biological letters, spelling out approximately 20,000 genes.

Each of these genes contains instructions telling a cell how to make a particular molecule (usually a protein), and it’s the particular combination of active genes that gives a cell its identity; for example, liver cells switch on genes that make digestive enzymes, brain cells activate genes that make neurotransmitters, and skin cells make sturdy keratin proteins to keep our insides in and the outside out.

The challenge of making sure the right genes are switched on in the right place at the right time is one of the most fundamental problems in biology; scientists have spent decades delving into the intricate processes that control gene activity.

This is where epigenetics comes in.

The invention of epigenetics is attributed to the British developmental biologist Conrad Waddington, who began using the word in the 1940s to explain how the cells in an embryo can adopt different fates – for example, becoming lung, liver or brain – even though they all have the same underlying genetic instructions. He took inspiration from the concept of epigenesis (“overgrowth”), which held that the various tissues of an embryo are derived from a single cell, in contrast to the discredited idea of preformation, where all the different parts are already laid down in miniaturised form.

Since then, the definition of epigenetics has expanded and is often back-translated to mean “above genetic”, more generally referring to the ways in which cells switch genes on or off. But there is no precise definition of the word – it’s used to describe several different things and there’s no scientific consensus about the correct meaning.

Some people take a broad view, referring to anything that affects development or physiology that isn’t written into the DNA code itself. Others take a strictly molecular definition of the term, using it to describe specific chemical modifications of DNA, or its packaging proteins, that are associated with certain patterns of gene activity.

One of the most well-studied epigenetic modifications is DNA methylation. In the 1940s, scientists discovered a different form of cytosine within mammalian DNA bearing a tiny chemical tag known as a methyl group, usually referred to as DNA methylation.

This modification was originally believed to be associated with inactive genes, leading to the idea that it’s the equivalent of a molecular “off switch”. But recent research shows that although specific patterns of DNA methylation are found in certain cell types and do seem to act as molecular Post-it notes of some sort, they are much more subtle and complex than previously thought.

One of the key principles that most researchers agree on is that epigenetic information must be heritable within an organism – cells should “remember” what has happened to them during their lifetime and perpetuate those patterns of gene activity as they grow and divide.

More controversially, scientists are now claiming that some epigenetic cues seem to perpetuate down the generations – known as transgenerational epigenetic inheritance.

Researchers have spent several decades trying to figure out exactly how the environment gets under the skin and exerts its effects on our genes. They have traditionally attacked the problem from opposite ends.

Molecular biologists have focused on mapping patterns of epigenetic modification (such as DNA methylation) in lab-grown cells, animal models or human tissue samples. Yet they have scant evidence linking any of these cellular changes to causes in the outside world or physical consequences further down the road.

Population researchers have come from the opposite direction, searching for environmental factors such as diet or socioeconomic status that correlated with physical or psychological outcomes. But they have been unable to make the molecular connection between them, instead invoking the more hand-waving version of “epigenetics” without any solid biochemical links.

Then came the rats.

In 2004, Canadian researcher Michael Meaney and his colleagues managed to join the dots. In a groundbreaking paper in the journal Nature Neuroscience, the team showed that rat pups born to mothers that spent a lot of time licking and grooming them were much better at handling stress than pups from less attentive mums. Intriguingly, the two groups of babies had small but significant differences in DNA methylation near a gene involved in responding to stress, which is normally active in the brain. Meaney found that the epigenetic changes were reversed if pups from inattentive mothers were fostered with more caring animals, and they also coped better with stress.

The results lit an epigenetic touchpaper, sparking overexcited headlines and triggering a whole new field of research. A flurry of papers came out over the following decade, cataloguing changes in DNA methylation in response to external influences in a range of lab animals. Meaney even extended his research to humans, showing that childhood abuse altered DNA methylation at a key stress-response gene and was associated with an increased risk of suicide later in life.

At long last, this seemed to be the missing biological link revealing how the environment talks to our genes and influences long-term behaviour in a flexible and reversible way.

An epigenetic education

Of course, this idea of epigenetic flexibility rather than genetic determinism is instinctively attractive to educationalists. If we can somehow hack our genetic blueprint and reconfigure particular genes to work in a better way, then this provides a way to explain, at a biological level, why changing the environment at home or school might make a big difference to educational outcomes.

One researcher at the forefront of efforts to bring the language and ideas of epigenetics into the world of social science is Deborah Youdell, professor of sociology of education at the University of Birmingham. For her, it’s all about coming up with hard biological evidence to show the effects of social situations and relationships on the body.

“The work by Michael Meaney demonstrates the capacity for gene activity to be changed over time,” she explains. “It throws out a fantastic challenge to what’s become established policy wisdom – that it’s too late to do anything in schools.

 

“There are people looking at translating that rat work into human populations, looking at parental care, sociology, cognitive behaviour and stress, particularly with relation to child development. [But] it’s also really important for us to bear in mind that humans live in way more complex situations than rats – that human parenting behaviour can’t be reduced to licking and grooming – so we have to proceed with caution.”

Youdell is particularly interested in the effect of stress on educational outcomes. She has pulled together a collection of molecular biologists, neuroscientists and analytical chemists to search for the epigenetic fingerprints of stress on the genome. It’s early days for the project, but she’s considering approaches such as looking at DNA methylation patterns in blood samples, or measuring the levels of certain chemicals in breath to get a measure of how the environment is affecting the body.

“I want to take seriously the possibility of understanding the underlying mechanisms,” says Youdell. “A process such as learning is very complex and there are multiple factors that influence learning – ranging from the macro scale of poverty that we can measure with economic indicators, through to the molecular function of neurons, which are influenced by sleep, diet and relationships inside and out of the classroom – and we need to put all of those things together.”

Scanning the genome

While Youdell is taking one environmental factor – stress – and seeing how it exerts its epigenetic effects on educational outcomes, other researchers are taking an alternative approach. At the University of Bristol, Neil Davies, Caroline Relton and their colleagues are searching for epigenetic modifications linking environmental influences to educational attainment.

In search of clues, they’ve scanned through the DNA of more than 10,000 individuals, looking at 450,000 sites across the genome that could be potentially methylated. Then they compared the methylation data with each person’s level of educational attainment, searching for patterns around specific genes that consistently matched up with particular outcomes and environmental factors. To their surprise, the only epigenetic differences that popped out were strangely familiar.

“The strongest correlation that came out in our analysis was whether the person smokes or their mother smoked during pregnancy, which has already been picked up in other studies as being linked to smoking behaviour,” explains Davies.

“This is something you might not expect if you’re looking for differences in behaviour that affect education, but it makes sense if people who leave school early are more likely to smoke – you’d expect to see epigenetic marks in the genome associated with smoking.”

In some ways this finding was reassuring, proving that the team’s methods were working correctly: smoking alters epigenetic marks and the chances of taking up smoking behaviour are already known to be associated with a few specific genes. But in terms of identifying previously unknown environmental and social factors that manipulate epigenetic marks and influence educational outcome, it was a bust.

“There’s a huge amount of excitement and interest in the broader social science field about epigenetics, but there is remarkably little hard data,” sighs Davies. “This is probably the biggest study to date, and what we’ve found is kind of obvious. It doesn’t suggest that there are enormous social effects there, so the idea that we’re going to go on to provide evidence for some of these ideas seems unlikely at this stage.”

So is the epigenetics craze over almost before it has begun? Although the results of this particular study may be disappointing to those searching for epigenetic explanations for educational outcomes, Davies has an important point to make about the data – or, more precisely, about where it comes from.

He and his team are studying patterns of epigenetic marks in blood samples, either taken from the umbilical cord at birth or drawn from adults. But education isn’t about the blood – it’s about the brain. While it’s relatively simple to get hold of a few drops of the red stuff, it’s virtually impossible for researchers to waltz into a classroom and start taking samples from children’s brains.

Academics differ on how important that access might be, though. Professor Frances Champagne at Columbia University, New York, started her scientific career working with Michael Meaney on his groundbreaking rat studies.

Today she runs her own lab, investigating how experiences in early life exert epigenetic effects on the brain and behaviour, and she has moved from animals to humans in search of answers.

“I was concerned at first when people started using blood or saliva for this kind of analysis, but for certain types of epigenetic outcomes you could rationally expect to see an effect in the brain and also in the peripheral blood,” she says.

However, for Professor John Greally, director of the Centre for Epigenomics at Albert Einstein College of Medicine in New York, our inability to see inside the epigenetic black box of the human brain is a major problem.

“We have to look at brains,” he says. “Brains are where all the action is happening. We have to do the science of epigenetics like we do in every other field and look at the tissue that’s involved. Most of the grant applications I see make no effort to look at the cell types that are actually relevant.”

Unfortunately, the one viable source of this essential material comes with its own set of issues. “Kids and adults die all the time,” says Greally. “There are brains, but there’s very little systematic collection of material for reasons of culture, squeamishness and more.

“People don’t want to offer this up, but it’s the sort of thing we need to drive as scientists – to say, ‘If the worst happens and your child dies, can I have a piece of their brain?’ It’s a tough ask but we’re never going to have meaningful-sized cohorts if we don’t do it.”

Greally also points out another problem with the rush to pin life outcomes onto epigenetic alterations: most large-scale experiments fail to take individual variations in the underlying genes into account. Although devotees of epigenetic ideas are drawn to the idea of an infinitely flexible and malleable brain, the meat computer in our skulls is still built by the actions of our genes, which vary from person to person.

“A lot of the stuff we’re calling epigenetic right now is actually driven by genetic variation,” he says. “There is a contribution from the genes that helps the brain to wire itself, and ways that epigenetic changes can override the genetic program to a certain extent. But the idea that there is no genetic influence is total crap.”

Handle with caution

So despite the intriguing data, big ideas and pseudoscientific marketing spiel, we’re actually still a long way from understanding how nature and nurture interact to make us who we are.

Youdell remains hopeful something will eventually come of the research. For her, the bringing together of biology and social science is helping to make a more convincing case for schools to look at their practices and think about their long-term effect on the body and brain.

“I’m not trying to lead us into a position where biological evidence is more powerful than educational evidence,” she says, “but I’m also realistic, and with some audiences the biological evidence may be more convincing. I think epigenetics offers us an opportunity to line some of that up in ways that may be really useful for education.

“If certain classroom environments and teaching methods are stressful and create chemical changes within the body that we recognise as having cognitive and health implications, is the response to that just to do some mindfulness, or should we ask where does this stress come from and why are we allowing this to be business-as-usual in schooling? Can we achieve similar outcomes without it being such a stressful place?”

Greally, too, says this is not an area to write off, but one to watch with caution.

“There is massive potential in this field, but don’t believe anything you’re reading right now,” he warns. “Treat everything as a preliminary result right now; they’re intriguing and potentially showing us something, but it’s not definitive. We have to hold things in reserve, not get too excited, and just watch this intriguing field develop.”

But Champagne fears we may already be on a path to over-eager early adoption of epigenetic research, including in the field of education. At a time when some commentators are trying to insist that genetic differences are always going to limit what schools can possibly hope to achieve, it’s useful to have scientific evidence to support the idea that nurture can override nature.

“Policymakers like the idea because it has the word ‘genetics’ in it,” she says.

“If you’re trying to make the case that you need a policy change or funds for a certain intervention programme, I think people are swayed by this kind of level of molecular analysis. I’m not suggesting that’s the right way to think about it, but I think that’s generally how people feel about these things – and if you’re an advocate for change, then you use what you can get your hands on.”


Kat Arney is the author of Herding Hemingway’s Cats: understanding how our genes work (Bloomsbury Sigma) and How to Code a Human (Andre Deutsch). She tweets @Kat_Arney

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