Recently, the Guardian published a story based on a scientific paper that claimed the stress experienced by Holocaust survivors somehow was detectable in their children through a process known as epigenetics. The paper was riddled with flaws: the scientists studied blood, which is a mixture of cell types, meaning there are any number of causes for the changes reported. The scientists only looked at a tiny subset of genes. They had an absurdly small sample size of 32 people, a tiny eight-person control group, who didn’t really look like good controls, and produced a contorted argument for why their data supported their original hypothesis. The paper probably shouldn’t have made it through to the scientific literature, and it certainly shouldn’t have made it to your Saturday breakfast reading. I don’t believe it and I’ll outline some reasons why below.

The scientific paper and newspaper story point to a rising interest in epigenetics. This is a seductive but rather slippery word that has come to mean a variety of things in relation to how molecular structures close to DNA work, in particular modification of DNA bases by methylation. It is certainly exciting, and has become a leading mechanism to explain how the environment communicates with our genes. But it’s also easy to oversimplify, and has been set up by some people as an inaccurate alternative to genetics.



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Coined before the discovery of DNA as the source of genetic information, the word “epigenetics” is now used in two way. Firstly, it can mean the ways in which modification or packaging of DNA results in the transmission of information within a group of cells. This is a well-established, evidence-based theory. However the second usage refers to the ways in which the modification or packaging of DNA might result in the transmission of information from one generation of people to the next, a theory for which there is not currently much evidence and which is therefore not well-established.

Trans-generational epigenetic inheritance – that is, environmentally-induced changes passed down from one generation to the next - is seen relatively often in plants. But it is far less common in mammals where its mechanism remains elusive. It is particularly difficult to show true trans-generational inheritance in humans. One reason is that a female foetus that is growing in the womb already carries its full complement of eggs. This means that there is physical DNA of any future grandchildren present inside every pregnant mother. This DNA is potentially being exposed to changes in the pregnant mother’s environment, so you need to look at least four generations down the line – to great grandchildren - to study true trans-generational inheritance in females. The male line is different: sperm are constantly being produced, and the cells which give rise to sperm develop all through the male’s lifetime, so seeing something go beyond two generations is interesting, in the absence of further environmental exposures.



Secondly, as one cannot fully control the breeding or physical environment of humans, there are many other far less exciting reasons why the great-grandchildren of one group of people may be different from the great-grandchildren of another. The complex societal forces that persist over time would be just one example. Even when studying mammals, such as mice, whose breeding and environment can be more controlled, true trans-generational epigenetic inheritance is extremely rare.



Epigenetics is also a well-established developmental mechanism that describes cellular memory during a person’s lifetime. Your skin cells, liver cells, neurons – in fact nearly all cell types - have the same genome tucked up inside. Yet each of them has a quite stable memory that tells them that they are skin, liver, or neurons and so forth, and that memory (largely) persists as cells multiply, even in petri dishes outside of the body. Understanding this epigenetic cell memory could help explain how previous life events or exposures in the environment might affect the current health and disease of one individual, and there are many scientists looking into this. Here genetics nearly always underlies these changing features of cellular memory - the theory of epigenetics is an excellent candidate for understanding how the environment and genetics combine, and many researchers are rightfully excited about exploring this further.

Why the broader public interest in epigenetics? I think it provides some fuel for the argument that genetics isn’t enough to explain why we are the way we are. Every week there seems to be a new piece of work associating genes with aspects of our everyday lives, from complex disease to more commonplace things, such as height, or the genetic heritability of GCSE results.

Many people bristle at these kinds of reports, both on a personal level and (for neurologists, psychologists and social scientists), on a professional level, as crude genetic determinism does not square with the very real lifestyle and societal events that have an impact on so many people. Without a doubt, we are far more than our genes, and geneticists (myself included) could do a lot better in communicating the somewhat fiendish complexity of our chosen field.



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In our defence, geneticists (like most people) often strive to simplify the world so they can focus on one thing at a time. We often separate problems into two simple components: the parts that can be attributed to genetics, and everything else. That everything else is, often (rather unhelpfully), called environment. For geneticists, environment is a catch-all term for all sorts of things, including personal actions, actions of others with passive effects, and the physical world in general, along with experimental or recording error. Furthermore, the statistical tests we use to sort out how much genetics and how much environment contribute to a disease or trait being studied focus on the things which change in the group of people being studied. Things which are relatively constant (such as the amount of sunlight, or access to good nutrition, the type of exams which are being set or access to antibiotics, say) might have a huge impact if they were changed, but the studies focus on what varies in the set of people being studied, not what is constant.



Take the example of the high heritability of success in GCSE English, from studying a cohort of teenagers going to English schools. If we set exactly the same English exam to a mixed group of teenagers from England and France, we’d discover that most of the variance in results is due to mother tongue, not genetics. Taking that insight further, if we changed the exam, or the teaching style, or course work vs exam, between English schools, we would get different results: the original study cannot assess the relative importance of things that are constant in it.

Why, then, are geneticists measuring these variables and applying these statistics? The resurgence of genetic studies has a lot to do with the fact that it is now shockingly cheap to obtain comprehensive genetic information about living things, including humans. There are both medical and research questions that can be studied with these more ubiquitous genomes. One medical reason is studying rare genetic diseases, which can have a big impact on individuals. Although each specific disease is rare, there are thousands of them, meaning that genetic disease affect up to 1 in 17 people in the UK. Cheap-ish genetic testing allows clinicians to better diagnose and sometimes provide far better treatment for patients with rare diseases, at the very least reducing the amount of testing and worry.

Another medical reason is that cancers are nearly always caused by persistent changes in a person’s DNA (which, as it happens, often cause mayhem in the epigenetics of their cells: the cancer’s cellular memory goes haywire). We now have a new way to characterise cancers that can improve the choice of treatment in some cases – and there is huge potential for more improvements using this in the future.

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I – and many others - are also interested in how genetics illuminates basic research. The statistical techniques can pinpoint genetic contributors to both disease and everyday features: for example, height, tonal perception, spelling proficiency - anything you can measure reliably. These studies can often find definitive evidence for which molecular machines are involved in all manner of biological phenomena. When they are successful, they provide a starting point for more precise investigations into how human attributes arise from molecules, no matter how complex the phenomena we are studying. Here the studies into the heritability of GCSE exam results would lead us towards the molecular machines which are somehow involved in aspects of performing well in these exams - an interesting starting point for more research.

This excitement about the unquestionable impact of our genes on rare disease, cancer and the ability to pin down many aspects of human life – from disease to behaviour – to molecular machines doesn’t mean genetics rules us. Indeed,for the vast majority of our lives, we make decisions that can have profound effects on ourselves and other people through changing our environment – diet, smoking, exercise etc. This is true on an individual and societal level, and it’s true for changes that have both good and bad effects.

We don’t need to challenge genetics – with epigenetics or anything else – to assert our control. Self-determination is not at odds with the genetic discoveries being made today. You are truly far more than your genes - your DNA is not your destiny.

Professor Ewan Birney is Director of the EMBL-European Bioinformatics Institute, based in Cambridgeshire UK, and tweets as @ewanbirney



