Family and Parenting 3-Book Bundle. Michael Reist

of these interlopers are a series of alkane molecules called methyl tags. Comprised of carbon and hydrogen, methyl tags latch onto our DNA, annexing the associated gene and discouraging it from coding. The more methyl molecules present, the less inclined the affected gene is to be transcribed. In this sense, methyl molecules act as a dimmer switch, their presence lowering a gene’s activity and, if attached in sufficient numbers, shutting it down entirely.

      Methylation, unlike genetic mutation, is completely reversible. A methylated gene will, if unmethylated, resume operating as if it had never stopped working in the first place. However, just because methylation is not necessarily permanent doesn’t mean that its influence on genes is fleeting. Methyl tags can stick with us for years, stowing away during cell replication and remaining in place for thousands of cell generations. Many of the methyl tags in your body right now have been there since you were born, and will stay there until you die. Your children will inherit some of them along with the 23 chromosomes with which you provided them (or will provide them, if said children are currently hypothetical).

      The idea of methyl molecules latching onto your DNA seems vaguely sinister, like tiny parasites hijacking your genome, but epigenetic marks are not only common, they’re downright essential to life. They can be found in every cell in the human body; are, in fact, the reason we have different cells in the first place.

      Each one of us begins life — in the loosest sense of the term — as a single cell called a zygote, which itself came from the fusion of two gametes (or sex cells): one sperm and one egg. Gametes are, in a sense, half cells, in that they possess only 23 of the typical 46 chromosomes present in every other cell in the human body.

      Upon formation, the zygote is almost entirely unmethylated, meaning that every gene present in its cells is unfettered and ready to code. This is a very good thing, because the zygote’s cellular offspring will go on to form every part of the human being it is destined to become, and every one of those genes will have its own part to play in the process.

      As the zygote divides, it begins to take the shape of a hollow sphere called a blastula. Blastula cells, like the original zygote cells, are unmethylated.[29] Every gene they possess is capable of transcribing its corresponding protein product.[30] Beyond this stage of development, that begins to change. The blastula cells continue to replicate, and eventually form multiple layers, each with a unique cellular destiny. The outermost layer, called the ectoderm, will become skin and nerves; the middle layer, or mesoderm, will become muscle and bone; the inner layer, or endoderm, will become internal organs.

      Development continues. The blastula becomes an embryo, which becomes a fetus, which grows and changes until it becomes a being capable of living outside the womb, at which point the mother goes into labour and gives birth to her baby, who in nine short months managed to transform from a single-celled organism into a complex, breathing, crying, nursing bundle of joy. Along the way, junior’s cells didn’t just divide; they specialized. Ectoderm became skin cells and nerve cells and brain cells. Mesoderm became muscle cells and bone cells and blood cells. Endoderm became stomach cells and liver cells and large intestine cells. And that specialization, though vital, comes at a price of flexibility.[31] Once an ectoderm cell becomes a skin cell, that’s it. Every cell it produces, and every cell those cells produce, and so on all down the line, will be a skin cell. It can’t double back and become a blood cell or a brain cell or a muscle cell. Its career path is set for life.

      Why do cells submit to such fatalism? Skin cells aren’t missing the requisite genes for becoming blood cells, or brain cells, or any cell you care to name. With a few exceptions — sex cells being the most obvious — every cell you possess contains all the genetic instructions needed to perform any job in the human body. What stops a blood cell from having a mid-life crisis of sorts and switching fields, becoming a skin cell or a liver cell or a neuron? In a word: methylation. By selectively methylating genes, cells can dedicate their finite resources to performing their assigned duties to the best of their ability. Having cells switch careers would not be beneficial to the organism in its entirety, which benefits from a rigid and highly codified division of labour.

      Think of each cell in your body as a tiny nanocomputer, and your DNA as the computer’s organic circuit board. The circuit board dictates the myriad processes responsible for keeping you alive, sending commands from the CPU, or nucleus, to the cell’s many components, regulating enzymes and releasing hormones and synthesizing data from your sensory inputs. Attached to this circuitry is a fuse box called the epigenome, a vast array of tiny methyl fuses, each linked to a distinct gene. Trip the switch and the gene falls silent, its current interrupted by a methyl tag. Remove the tag by reinstating the fuse and the gene comes back into play, its semiconductors alight with a fresh thrumming of energy. It doesn’t matter if the fuse was turned off for five minutes or five years; a flick of the switch is all it takes to get things running again. By contrast, rewiring genetic circuitry is cumbersome, dangerous, and permanent, the result of rogue molecules haphazardly soldering wires and scraping down bits of silicon — in short, mutations. Occasionally, by pure serendipity, these changes allow the machine to function more efficiently at its particular task. Far more often they are disruptive and damaging, and tiny molecular technicians must be called in to fix them.

      Unlike genetic mutations, which are accidental and unpredictable, epigenetic tags are easy for the body to regulate. They assure that the most useful circuits get sufficient energy and any processes working contrary to the cell’s goal are silenced, streamlining efforts and increasing efficiency.

      Tabula Rasa

      Epigenetic effects are not always as predictable as those that determine which cells get which job. Some are downright bizarre. Consider the agouti mouse, an animal intent on proving the misnomer inherent in the term “genetically identical.” For though the genotypes of two agouti mice can be indistinguishable down to the last nucleotide, their phenotypes[32] often appear to be anything but. In adulthood, some have grey-brown coats and svelte physiques, while others have yellow coats and great, rotund bellies. The fat and yellow mice not only suffer from decreased mobility, but also from an increased risk of developing diabetes and cancer. The difference between them and their slim counterparts is the agouti gene, identical in both but only active in the fat mice. In the slim mice the agouti gene is highly methylated, keeping it from producing its affiliated protein; in the fat mice the gene is unmethylated and codes freely, accounting for both the affected mouse’s yellow coat and its corpulent frame.

      Having discovered this distinction, the obvious question is what causes it? There is no one culprit, though exposing pregnant mice to bisphenol A — a chemical compound found in a number of plastic products, including, alarmingly, baby bottles — has been found to increase the frequency at which their infants are born with their agouti genes unmethylated. The unmethylated agouti mice are more likely to sire offspring whose agouti genes are also unmethylated, compounding the disorder. Happily, this problem has a remarkably easy fix: feeding mothers pellets laced with methyl molecules greatly reduces their offspring’s chance of having an unmethylated agouti gene. What’s more, when mice who have had their agouti gene “fixed” sire children of their own, the next generation retains the correction despite never having been fed the methyl pellets themselves.

      Bearing this research in mind, the effects of the Dutch Hunger Winter no longer seem quite so mysterious. As with agouti mice, pregnant women experiencing the famine gave birth to children with an epigenetic predisposition to a number of adverse conditions, including — again, as with agouti mice — obesity, heart disease, and diabetes. And the famine’s effects didn’t stop at that generation. The Hunger Winter study continues to this day, and researchers still find traces of the famine’s impact on the descendants of those who suffered through it.

      Unfortunately, one detail the agouti mice and Dutch Hunger Winter studies do not share is a tidy and easily remedied epigenetic cause. There is no agouti-like gene in humans solely responsible for the intergenerational ramifications of famine, no simple solution obtainable through a judicious addition or removal of a few methyl molecules. There are likely a number of genes at play,[33] some which should be methylated but aren’t, and others that shouldn’t be methylated but are. And even if we developed technology capable of tracking down and altering each offending gene and methyl tag, we couldn’t say for sure that “correcting”