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But what was thrown up by these sessions and the research carried out on the twins left geneticists puzzled. Instead of finding a dozen or so genes for common conditions such as obesity, researchers found that hundreds were involved. “In the case of osteoporosis, which we once thought was caused by a single mutant gene, we now believe that there may be 500 genes involved – interacting to trigger the disease in people at different ages,” says Spector.

“These are genes that individually only account for 0.1% of susceptibility for a condition. And even then, these genes, in total, only seem to account for a fraction of the variance we see in the prevalence and severity of these conditions in the population. This phenomenon has a name: it is called missing heritability.”

It is an effect you can see directly from the studies of identical twins carried out at St Thomas’. “We now began to look not at the similarities between identical twins but the differences. It was a shift in perception really. Our work shows that the heritability of your age at death is only about 25%. Similarly, there is only a 30% chance that if one identical twin gets heart disease the other one will as well, while the figure for rheumatoid arthritis is only about 15%.”

It is a baffling observation: individuals with identical genes and often very similar conditions of ubringing but who experience very different life outcomes. What could be the cause? The answer, says Spector, came to him in a Damascene moment four years ago. The causes of these differences were due to changes in the human epigenome, he realised.

“Essentially, epigenetics is the mechanism by which environmental changes alter the behaviour of our genes,” he says. “This involves a process known as methylation, which occurs when a chemical known as methyl, which floats around the inside of our cells, attaches itself to our DNA. When it does so, it can inhibit or turn down the activity of a gene and block it from making a particular version of a protein in our bodies.” Crucially, all sorts of life events can affect DNA methylation levels in our bodies: diet, illnesses, ageing, chemicals in the environment, smoking, drugs and medicines.

Thus epigenetic changes produce variation in disease patterns. And recent experiments carried out by Spector and his colleagues, in which they have looked at methylation levels in pairs of identical twins, back the theory. “We have studied identical twins who have different tolerances to pain and shown that they have different states of methylation. We have also produced similar results for depression, diabetes and breast cancer. In each case, we have found genes that are switched on in one twin and switched off in the other twin. This often determines whether or not they are likely to get a disease.”

Epigenetic changes are not just simple environmental changes, however. They influence a person’s genes and can have an effect that can last for two or three generations in extreme cases. For example, studies of the children and grandchildren of pregnant women who endured starvation in the second world war and in China in the 50s have revealed they tended to be smaller and more prone to diabetes and psychosis. These trends are put down to epigenetic changes.

“Essentially, they are a way to make short-term changes to a generation,” says Spector. “A famine strikes but you cannot instantly alter your genes. But epigenetic changes allow you to produce children who are fatter or skinnier or whatever is best suited to the new circumstances. These changes will last for at least two or three generations, by which time you would hope the change in the environment will have passed. It may not, of course.”

-Robin McKie, “Why do identical twins end up having different lives?The Guardian. 1 June 2013.

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