On reflection Postgrad Med J: first published as 10.1136/postgradmedj-2016-133993 on 25 February 2016. Downloaded from

fur instead of brown. In another much for dummies quoted experiment, researchers claimed to show that mice bred from fathers who John Launer had been trained to become afraid of a particular smell also showed avoidance of the same smell – although it is hard to In the last few years, epigenetics has mechanisms themselves are very common understand how such a specific outcome seized the public imagination. Magazines in , quite aside from environmental could be achieved through known New Scientist fl like are publishing articles in uences, and they govern expres- molecular mechanisms.9 “ with titles such as How to change your sion in all kinds of ways, including As far as human beings are concerned, ” 1 by changing your lifestyle . A turning a stem into a liver or a skin everyone has known for a long time that book called “The Epigenetic Revolution” cell, or a bee larva into a worker or a 2 maternal behaviour during has become a bestseller. The popular queen bee. One hypomethylating agent, affects the growing fetus, with lifelong press regularly reports epigenetic research, decitabine, is an established treatment for effects. The most familiar example is including a recent study purporting to myelodysplastic disorders. probably foetal alcohol syndrome, where show that severe psychological trauma can The question then arises: do environ- a mother’s can lead to irrepar- ’ 3 be passed down through one s genes. mental effects have to happen anew in able damage to her infant. Although this Overall, it would be easy for anyone now- each generation, or could they ever be probably happens through epigenetic adays to form the impression that the passed down from one generation to the mechanisms, there is no evidence that genetic destiny of future generations is next? The French Larmarck effects like these are transmitted to a entirely in our own hands, DNA is highly argued a long time ago that acquired further generation without repeated envir- malleable, and Darwin and Mendel have characteristics could be transmitted. onmental influences as well. For a while, been thoroughly discredited. In this Indeed, he believed quite wrongly that it was believed that prolonged maternal article, I want to try and bring epigenetics this was the sole basis of inheritance. starvation could lead to long term transge- back down to earth, with a simple More surprisingly, Darwin also thought it nerational effects, but this has now been account of what it is and is not, and what could sometimes happen. As well as his called into question.10 epigenetic research has and has not shown theory of , based on random One epidemiological study has shown so far. followed by natural that fathers who smoked before adoles- fi Epigenetics is best de ned as the study selection, he also suggested that lifetime cence were more likely to have sons with “ ” of changes in organisms brought about by experiences could create gemmules a higher body mass index.11 However, no fi modi cation of , rather which attached themselves to eggs and similar result has been shown in daugh- than by alteration of the in sperm, and affected offspring as a direct ters, there is no molecular evidence to “ ” 4 the form of DNA. The term epigenetic result. It seemed an interesting idea at support the finding, and social effects may ’ was originally coined in the 1950s, and the time, but after Mendel s discovery of also have played a part. There are a few used to denote the way that genes interact the principal laws of inheritance, biolo- very rare inheritable conditions, where with the environment, in order to gists lost interest in this possibility. the underlying defect in some individuals produce each individual . To may lie with rather than describe this process at its simplest: you TRANSGENERATIONAL EPIGENETICS DNA, but these are highly exceptional may be born with a capacity to be tall and The first hints that acquired characteristics and hard to interpret.12 The more spec- fi http://pmj.bmj.com/ con dent, but if you are undernourished might be transmissible after all were tacular findings that reach the headlines and abused as a child, you are likely to rather prosaic. In the 1950s, a plant gen- often appear to confuse correlation with turn into a stunted and fearful adult eticist named RA Brink showed that cross- causation, make claims that bear little rela- instead. There is nothing very remarkable ing a dark form of with a mottled tion to the evidence, are based on samples about the way genes interact with the form appeared to render the dark too small to reach statistical significance, environment in this way. Concepts like permanently inactive.5 This alteration per- or report results selectively.13 There may gene expression and plasticity have been sisted for hundreds of generations – a still be some exciting findings ahead of us on October 2, 2021 by guest. Protected copyright. commonplace in for a long time, process aptly called “”.We in the epigenetics, beyond what happens and indeed form the basis of all modern now know that this and similar forms of to laboratory mice in extremely unusual biological thinking. non-Mendelian inheritance are brought tests, but we aren’t there yet. Since genes alone do not determine about by substances that pass down in the , mechanisms have to exist at gametes, alongside DNA. These are EPIGENETIC HYPE the molecular level in order to mediate mainly RNA , but also include Given this state of affairs, it is worth gene-environment interactions. As soon as and .6 Similar effects have asking why epigenetics is having such an some of these mechanisms were discov- been shown in animal experiments, impact on people’s imagination. Part of “ ” ered, the term epigenetics came to be although they are not nearly as frequent the answer is that Darwin’s theory of applied to them as well. The best known or dramatic as you might believe, and , with its vast time scale, of these is methylation, where a methyl their significance in natural conditions is immensely slow progress, and seemingly group binds to on a stretch of far from clear.7 For example, when preg- improbable consequences like the human DNA, and renders it less active. The nant mice are fed with Bisphenol A, a eye, is still too challenging for many toxic ingredient of plastics, the resulting people to grasp. It is far easier to seize on adverse effects appear not only in their an idea like the rapid alteration of genetic Correspondence to Dr John Launer, Faculty offspring but also in the following gener- material, than a theory that feels counter- , Health Education England, Stewart 8 House, 32 Russell Square, London WC1B 5DN, UK; ation. These include , , an intuitive if you only expect to be alive for [email protected] increased frequency of , and yellow around 80 years, rather than a few

Launer J. Postgrad Med J March 2016 Vol 92 No 1085 183 On reflection Postgrad Med J: first published as 10.1136/postgradmedj-2016-133993 on 25 February 2016. Downloaded from million. There is also a common misap- Twitter Follow John Launer at @JohnLauner 7 Morgan DK, Whitelaw E. The case for prehension that modern biology strongly transgenerational epigenetic inheritance in humans. “ Mamm 2008;19:394–7. supports the view that genes are 8 Morgan HD, Sutherland HE, Martin DIK, et al. destiny”, however much real do Epigenetic inheritance at the agouti locus in the to debunk this.14 People therefore reject mouse. Nat Genet 1999;23:314–8. mainstream , without ever having To cite Launer J. Postgrad Med J 2016;92:183–184. 9 Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in understood it in the first place. Probably – Postgrad Med J 2016;92:183 184. subsequent generations. Nat Neurosci 2014;17: most important of all, the hype around doi:10.1136/postgradmedj-2016-133993 89–96. epigenetics boosts people’s sense of 10 Stein AD, Lumey LH. The relationship between control: if you believe you can change REFERENCES maternal and offspring birth weights after your own genes, or at least those of your 1 How to change your genes by changing your maternal prenatal famine exposure: the Dutch lifestyle. New Scientist, 9 Dec 2015. https://goo.gl/ Famine Birth Cohort Study. Hum Biol 2002;72: children, you may feel less of a prisoner – HgVmqV (accessed 21 Jan 2016). 641 54 to the arbitrary effects of your genome, or fi 2 Carey N. The Epigenetics Revolution: How Modern 11 Pembrey ME, Bygren LO, Kaati G, et al. Sex-speci c, your own upbringing. Epigenetic hype Biology is Rewriting Our Understanding of Genetics, male-line transgenerational responses in humans. Eur – feeds into the same rugged, individualistic Disease and Inheritance. London, Icon Books, 2012. J Hum Genet 2006;14:159 66. vision of self-improvement as the dozens 3 Rouse A. Holocaust survivors pass the genetic 12 Buiting K, Gross S, Lich C, et al. Epimutations in Prader-Willi and Angelman syndromes: a molecular of popular books and hundreds of maga- damage of their trauma on to their children, researchers find. Mail Online, 21 Aug 2015 http:// study of 136 patients with an imprinting defect. Am zine articles on , explaining J Hum Genet 2003;72:571–7 15 www.dailymail.co.uk/sciencetech/article-3206702/ how you can change your own brain. Holocaust-survivors-pass-genetic-damage-trauma- 13 Mitchell K. The trouble with epigenetics (Part 2). The irony in all of this is that the children-researchers-find.html (accessed 21 Jan Wiring the Brain [blog], 14 Jan 2013. http://www. 2016). wiringthebrain.com/2013/01/the-trouble-with- lessons being drawn in the hyped articles epigenetics-part-2.html (accessed 21 Jan 2016) are usually true in their own right, even if 4 Darwin C. The Variation of Plants and Animals Under Domestication. London: John Murray. 1868: 14 Laland K, Brown G. Sense and Nonsense: the arguments used to support them are 375. Evolutionary Perspectives on Human Behaviour, 2nd unsound. It certainly makes good sense to 5 Brink RA. Paramutation at the R locus in maize edition. Oxford: Oxford University Press, 2011. provide everyone with good , a plants trisomic for 10. Proc Natl Acad 15 Neuroskeptic. Epigenetics: Are genes the new brains? Discover Magazine, 26 Sep 2013 http://blogs. stable upbringing, and a secure social Sci 159;45: 819–27. 6 Rando OJ. Ghosts in the genome: How one discovermagazine.com/neuroskeptic/2013/09/26/ environment, but one scarcely needs an generation’s experience can affect the next. The the-social--of/ (accessed 21 Jan 2016). understanding of molecular epigenetics to Scientist, 1 Dec 2015. http://goo.gl/nfIdVc (accessed be convinced of this. 21 Jan 2016) http://pmj.bmj.com/ on October 2, 2021 by guest. Protected copyright.

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