Even more extraordinarily, some of these effects seem to be present in the children of this group, i.e. in the grandchildren of the women who were malnourished during the first three months of their pregnancy. So something that happened in one pregnant population affected their children’s children. This raised the really puzzling question of how these effects were passed on to subsequent generations.
Let’s consider a different human story. Schizophrenia is a dreadful mental illness which, if untreated, can completely overwhelm and disable an affected person. Patients may present with a range of symptoms including delusions, hallucinations and enormous difficulties focusing mentally. People with schizophrenia may become completely incapable of distinguishing between the ‘real world’ and their own hallucinatory and delusional realm. Normal cognitive, emotional and societal responses are lost. There is a terrible misconception that people with schizophrenia are likely to be violent and dangerous. For the majority of patients this isn’t the case at all, and the people most likely to suffer harm because of this illness are the patients themselves. Individuals with schizophrenia are fifty times more likely to attempt suicide than healthy individuals[2].
Schizophrenia is a tragically common condition. It affects between 0.5 per cent and 1 per cent of the population in most countries and cultures, which means that there may be over fifty million people alive today who are suffering from this condition. Scientists have known for some time that genetics plays a strong role in determining if a person will develop this illness. We know this because if one of a pair of identical twins has schizophrenia, there is a 50 per cent chance that their twin will also have the condition. This is much higher than the 1 per cent risk in the general population.
Identical twins have exactly the same genetic code as each other. They share the same womb and usually they are brought up in very similar environments. When we consider this, it doesn’t seem surprising that if one of the twins develops schizophrenia, the chance that his or her twin will also develop the illness is very high. In fact, we have to start wondering why it isn’t higher. Why isn’t the figure 100 per cent? How is it that two apparently identical individuals can become so very different? An individual has a devastating mental illness but will their identical twin suffer from it too? Flip a coin – heads they win, tails they lose. Variations in the environment are unlikely to account for this, and even if they did, how would these environmental effects have such profoundly different impacts on two genetically identical people?
Here’s a third case study. A small child, less than three years old, is abused and neglected by his or her parents. Eventually, the state intervenes and the child is taken away from the biological parents and placed with foster or adoptive parents. These new carers love and cherish the child, doing everything they can to create a secure home, full of affection. The child stays with these new parents throughout the rest of its childhood and adolescence, and into young adulthood.
Sometimes everything works out well for this person. They grow up into a happy, stable individual indistinguishable from all their peers who had normal, non-abusive childhoods. But often, tragically, it doesn’t work out this way. Children who have suffered from abuse or neglect in their early years grow up with a substantially higher risk of adult mental health problems than the general population. All too often the child grows up into an adult at high risk of depression, self-harm, drug abuse and suicide.
Once again, we have to ask ourselves why. Why is it so difficult to override the effects of early childhood exposure to neglect or abuse? Why should something that happened early in life have effects on mental health that may still be obvious decades later? In some cases, the adult may have absolutely no recollection of the traumatic events, and yet they may suffer the consequences mentally and emotionally for the rest of their lives.
These three case studies seem very different on the surface. The first is mainly about nutrition, especially of the unborn child. The second is about the differences that arise between genetically identical individuals. The third is about long-term psychological damage as a result of childhood abuse.
But these stories are linked at a very fundamental biological level. They are all examples of epigenetics. Epigenetics is the new discipline that is revolutionising biology. Whenever two genetically identical individuals are non-identical in some way we can measure, this is called epigenetics. When a change in environment has biological consequences that last long after the event itself has vanished into distant memory, we are seeing an epigenetic effect in action.
Epigenetic phenomena can be seen all around us, every day. Scientists have identified many examples of epigenetics, just like the ones described above, for many years. When scientists talk about epigenetics they are referring to all the cases where the genetic code alone isn’t enough to describe what’s happening – there must be something else going on as well.
This is one of the ways that epigenetics is described scientifically, where things which are genetically identical can actually appear quite different to one another. But there has to be a mechanism that brings out this mismatch between the genetic script and the final outcome. These epigenetic effects must be caused by some sort of physical change, some alterations in the vast array of molecules that make up the cells of every living organism. This leads us to the other way of viewing epigenetics – the molecular description. In this model, epigenetics can be defined as the set of modifications to our genetic material that change the ways genes are switched on or off, but which don’t alter the genes themselves.
Although it may seem confusing that the word ‘epigenetics’ can have two different meanings, it’s just because we are describing the same event at two different levels. It’s a bit like looking at the pictures in old newspapers with a magnifying glass, and seeing that they are made up of dots. If we didn’t have a magnifying glass we might have thought that each picture was just made in one solid piece and we’d probably never have been able to work out how so many new images could be created each day. On the other hand, if all we ever did was look through the magnifying glass, all we would see would be dots, and we’d never see the incredible image that they formed together and which we’d see if we could only step back and look at the big picture.
The revolution that has happened very recently in biology is that for the first time we are actually starting to understand how amazing epigenetic phenomena are caused. We’re no longer just seeing the large image, we can now also analyse the individual dots that created it. Crucially, this means that we are finally starting to unravel the missing link between nature and nurture; how our environment talks to us and alters us, sometimes forever.
The ‘epi’ in epigenetics is derived from Greek and means at, on, to, upon, over or beside. The DNA in our cells is not some pure, unadulterated molecule. Small chemical groups can be added at specific regions of DNA. Our DNA is also smothered in special proteins. These proteins can themselves be covered with additional small chemicals. None of these molecular amendments changes the underlying genetic code. But adding these chemical groups to the DNA, or to the associated proteins, or removing them, changes the expression of nearby genes. These changes in gene expression alter the functions of cells, and the very nature of the cells themselves. Sometimes, if these patterns of chemical modifications are put on or taken off at a critical period in development, the pattern can be set for the rest of our lives, even if we live to be over a hundred years of age.
2
A useful starting point for descriptions of the symptoms of schizophrenia, its effects on patients and their families, and relevant statistics is www.schizophrenia.com