On Epigenetics

Richard C. Francis on his new book, Epi-Genetics: The Ultimate Mystery of Inheritance - HERE (I am still tempted think of epigenetics as the science of Karma):

"Changes that arise from normal gene regulation happen in the short term, but epigenetic changes alter the way that genes react to the world for a very long time—even when the original cause has vanished. It is this rather shocking long-term influence that makes epigenetics one of most alluring—and terrifying—shifts in how we think about our genes. Epigenetic changes can occur in adulthood, in childhood, even in utero (a phenomenon explained in Origins by Annie Murphy Paul), with the consequence that an event you experienced as a child could dictate the ways your genes behave in a different situation as an adult. It may have been simple-minded to assume that we are programmed by our genes, but there was a weird egalitarianism in that: Even if we get different genes to begin with, we are under their sway in the same way. Epigenetic change means that not only do we start out as unwitting participants in a genetic lottery, but environmental forces we cannot see or control can mess with our genetic hardware and change our destiny. At the level of DNA, epigenetic change occurs when particular chemicals become attached to the gene, and stay there, altering how the gene behaves. The first of these attachments to be discovered, and still the best known, is from the methyl group. In 1980, it was shown that different degrees of methylation can alter gene expression in different ways. Demethylation can cause problems, too. Depending on the genes involved, one consequence can be unconstrained cell division, otherwise known as cancer. 

The causes of epigenetic attachments are various, and the evidence so far indicates they range from pollution to stressful social interactions. Studies on the long-term effects of a pregnant woman's poor nutrition suggest that the food our mothers eat while we are in the womb can shape our gene expression. So, too, the food they don't eat. The best data on long-term genetic change come from the terrible Dutch famine of 1944, when the Nazis blockaded food supplies, disrupted transport, and flooded farmlands in western Holland. It has emerged as the classic case study in the field, thanks to the exemplary record-keeping of the Dutch, which gives researchers solid longitudinal data on the famine's many far-reaching effects. For children who were in utero at the time of the famine, the consequences include a higher risk of schizophrenia, antisocial personality disorder and other psychological disturbances, and even 50 years down the road, a greater likelihood of becoming obese. At first glance it may seem that the legacy is poor health in general. But that's not how it works. The impact depends on exactly when the fetus was exposed to the famine, Francis reports. Women whose mothers suffered the famine in the first trimester have a higher risk of breast cancer. Those whose mothers suffered in the second trimester have problems with lungs and kidneys.

In 2009, one team unearthed a tantalizing result: Examining the blood cells of adults who were in the womb at the time of the famine, researchers discovered unusual epigenetic attachments on the gene that codes for a hormone called insulin-like growth factor 2. The hormone is crucial for growth, particularly in fetuses. It turns out the IGF2 gene of the famine group is methylated to a different degree than the same gene in a non-famine group. Even though scientists haven't yet traced the specific causal chain between the epigenetic attachments, the genes, and people's lives, those attachments are a smoking gun for epigenetic change in the womb, and health issues many decades later.

Even more fascinating, and unnerving, it appears that the consequences of epigenetic change may stretch over several lifetimes. In one Swedish village, which also has records of crop harvests that go back hundreds of years, the paternal grandsons of men who experienced famine were less likely to have cardiovascular disease than their peers whose paternal grandfathers did not experience famine. But, wait, conventional wisdom says only genes are supposed to be passed on to the next generation. Most epigenetic attachments are stripped away from genes in the creation of sperm and egg cells. Yet it seems that a record of some epigenetic attachments is passed on and then recreated in the genome of the embryo, too. That means that an event in your parent's life that occurred before you were conceived could affect how your genes work today. In other words, the sins of the fathers may be visited on the deoxyribose nucleic acids of the sons. How malleable are our sons and daughters? The mechanisms involved are extraordinarily subtle. Researchers are now only beginning to understand how and why this happens.