Epigenetics, a word that seems to have stirred up disagreement between scientists for so long, is currently experiencing a rebirth and may have applications for the prevention of many different human diseases.
Starting at the beginning, the word ‘epigenesis’ was coined by the Greek philosopher Aristotle over 2,200 years ago because he was sick of the theory current at the time that we all start out as microscopic versions of our adult selves. He believed that all complex creatures grow from a simple fertilised egg or seed though to a mature organism through stages of development and differentiation: out of the simple comes the complex. This idea is widely accepted as true today.
Step forward another 75 years and followers of Darwin thought they knew it all – evolution occurs by natural selection through random changes in our DNA that have enabled us evolve and adapt over millennia. And that’s that. Then Conrad ‘Hal’ Waddington came along and stirred things up by turning ‘epigenesis’ to ‘epigenetics’, which he used to describe the way in which our genes interact with their environment to make us what we are. In this sense, epigenetics means literally ‘the factors on top of our genes’. Waddington was a man before his time. Between then and now, arguments have raged about whether nature (genes) or nurture (environment) are more likely to influence our health and behaviour. The truth, exemplified by a recent book by Matt Ridley entitled ‘Nature via Nurture: Genes, experience and what makes us human’ is, like Waddington suggested, a combination of the two.
Arguments aside, epigenetic changes are most likely lie behind a recently recognised phenomenon call the Developmental Origins of Health and Disease. Known in short as ‘DOHaD’, the idea is that our experiences in the womb and early childhood can ‘program’ our future health. It is likely that epigenetics is part of the programming language involved. An oft-cited example of this in humans is that sixty-year-olds who were in their mother’s womb at the time of the Dutch Famine in the Second World War, not only had poorer heart health than their siblings but also had an epigenetic imprint of this experience stamped on a handful of their genes.
Animal studies reveal a similar story. In rats, a mother’s licking and grooming behaviour influenced subsequent stress levels in the offspring, mediated by an epigenetic change to a gene involved in stress response. Newborn rat pups whose mothers spend time licking and grooming them grow into calmer adults, whilst pups who receive little maternal attention tended to grow into more anxious adults. Grooming altered the pattern of epigenetic marks, which in turn altered gene activity of the stress regulator gene. Critically, when neglected rats were treated with a drug that alters these epigenetic marks, both their anxiety and the accompanying epigenetic changes could be reversed.
Such findings have huge implications for medicine, the largest being that if we can reliably detect epigenetic changes that in early childhood signal a risk for diseases such as cancer, heart disease, autism or diabetes, we can start to prevent these diseases by intervening early. This is the area I find most exciting, but we have a long way to go to the clinic for most of these. However, we can take heart from cancer research, which has already supplied a small number of epigenetic tests that can predict severity or response to treatment in some cancers.
Finally, it seems that in principle, Lamarck and Darwin may also have been on the right track after all. There is accumulating evidence that the environment our mothers and even our fathers encountered before we were a twinkling in their eye may be passed onto us in the form of a risk for conditions such as obesity, diabetes or anxiety. Studies of a remote Swedish village have shown that food abundance in grandparents correlate with the health of their grandchildren. Another found that sons of men who smoked just before puberty were more likely to become obese. However, neither of these has yet been linked with an epigenetic change. Could it be that epigenetic marks can ‘leak though’ to us via eggs and sperm? There is recent evidence that this can happen in animals that has people in some very high places invoking Lamarck.
‘Epigenetics explained‘ by Scientific American
Awesome animations and short documentaries
‘Lick your rats‘ interactive game from the Epigenetics Genetic Science Learning Center, University of Utah (takes about 5 mins to lick a couple of rats)
‘Epigenetics Overview‘ by Cell Signaling Technologies (02:14)
‘Epigenetics‘ – a short documentary from the Science Show on DNATube (09:26)
Articles – basic
‘Epigenetics’ by Brona McVittie (2006)
Articles aimed more at undergraduates