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” the problem wouldn’t cause another more serious ailment to appear in a different system or organ. After all, who could’ve guessed that the same gene responsible for producing yellow pigment in mouse hair also leads to chronic obesity?
Ultimately, the findings of the agouti mice and Hunger Winter studies are less about developing a solution and more about reinventing the way we look at the problem. Epigenetics is a new science, but it has undergone a substantial shift within its short lifetime, and studies like the agouti mouse experiment have been at the helm of this change.
According to conventional genetic theory, inheritance consists of 46 chromosomes passed from parents to their child, 23 from mom and 23 from dad. That’s it. Geneticists acknowledge that nurture is important as well, but its work begins after genes have already spent a full nine months doing their thing. Sure, environmental influences are in a broad sense inherited (since mothers teach children who become mothers who then teach their own children, etc.), but such inheritance is subject to a number of conditional clauses and assumptions (children aren’t adopted, parents raise their children in a manner analogous to how they themselves were raised, etc.) that make them inconsistent and unreliable. Genes, say geneticists, are stalwart messengers, grimly striding through the harshest conditions in unwavering pursuit of their goal: passing their vital chromosomal missives on to the next generation. The environment shifts and slides and changes like the weather. Genes are sturdy as stone.
Except that we are garnering more and more evidence that implies this might not be the case. Environmental influences may not be as capricious as once assumed; indeed, they may stick to our genes for generations. And epigenetics provides the glue that holds them in place.
In its earliest incarnation, epigenetics was not expected to adopt that sort of role. Its methyl tags, though vitally important to proper gene expression, were thought to remain only on the genes of the individual, and not be passed along with the rest of their genetic legacy. The zygote, with its absolute cellular potential, was supposed to be a kind of blank state, the dry-erase epigenetic scribblings of previous generations wiped clean, leaving 46 unadulterated chromosomes ready to be methylated again from scratch. Yet somehow epigenetic information is being inherited. To understand how this happens, we need to think of inheritance as more than a molecular transaction.
Umbilical Telegraphs
Unlike with genes, we haven’t yet developed a satisfactory theory as to why and how epigenetic inheritance occurs. We do know, however, that certain epigenetic traits have critical periods where an action or chemical or experience is especially likely to trigger a long-term change in a gene’s methyl pattern. Often, these critical periods can be found early in a person’s life, particularly when they’re still in the womb. During the Hunger Winter, for instance, the gender and gestational period of affected fetuses determined what condition they would be predisposed to as they grew. Women whose mothers experienced famine during the first trimester of their pregnancy were twice as likely as the normal population to develop schizophrenia. For men, having a mother who experienced famine during the first two trimesters of their pregnancy greatly increased their odds of becoming obese; if the famine extended well into the third trimester, they faced the opposite problem, becoming chronically underweight. These conditions were highly gender specific; women showed no spike in obesity, nor did men show an increase in their odds of developing schizophrenia as a result of early exposure to famine.
Things get stranger still. Consider two genetic disorders, Angelman syndrome and Prader-Willi syndrome. On the surface, they don’t seem to have a lot in common. People with Angelman syndrome have severely reduced cognitive function, lacking the ability to say more than a few simple words. Their movement is clumsy and irregular, marked by jerks and tremors. Yet for all the adversity they face, people with Angelman syndrome — informally called “angels” — are almost universally happy. Their faces alight with beatific smiles. Giggles cascade constantly from their lips, often accompanied by a joyous and endearing flapping of their hands. Indeed, it was the grouping of these characteristics — the smiling, angelic features and erratic, jerky movements — that inspired Dr. Harry Angelman’s original name for the disorder: happy puppet syndrome (the name was eventually changed, as it seemed patronizing).
Compared to “angels,” individuals with Prader-Willi syndrome are far less mentally impaired. Their biggest challenge is in the physical realm. Prader-Willi sufferers have insatiable appetites. They also store fat at unusually high rates. By their teenage years, individuals with Prader-Willi syndrome often become morbidly obese, and those who don’t remain highly susceptible to substantial weight gain for their entire lives.
The Angelman and Prader-Willi syndromes could scarcely be more different. Yet both of these conditions are caused by a partial deletion of chromosome 15, meaning a section of the chromosome was either badly damaged prior to conception or was never present in the sperm or egg in the first place. What’s more, the deletion in both cases is not simply on the same chromosome, or overlapping. It is identical. The exact same genetic defect, down to the last missing nucleotide, causes two completely unrelated syndromes. And the allocation of each syndrome is in no way random; it depends solely on which parent supplied the offending chromosome. If inherited from the father, the deletion causes Prader-Willi syndrome; if inherited from the mother, it causes Angelman syndrome.
It’s difficult to articulate to anyone who is not a biologist how big an upset this is to the understanding of genetic inheritance. Imagine learning that water sometimes flows uphill or gravity takes the odd holiday. A chromosome’s lineage wasn’t supposed to matter. Genes were just genes, and they did their job regardless of where they came from. Yet the Angelman and Prader-Willi syndromes, the Dutch Hunger Winter study, and the agouti mouse experiments all suggest that we don’t have nearly as full a grasp on how inheritance works as we once believed. And there’s no reason to believe these examples are isolated phenomena and not part of a larger trend. Hedonistic pursuits once thought to harm only those who participated in them — smoking, drinking alcohol, eschewing sleep for another night out with friends, eating burgers with unsettlingly honest names like “the Artery Clogger” — might actually be worming their way into subsequent generations. The dangers of fetal alcohol syndrome and smoking during pregnancy have thankfully become well-known, but epigenetic inheritance, it seems, can draw from experiences occurring outside that critical nine-month window.
Our intention is not to send you screaming to the nearest monastery for a life of unyielding austerity. Nor are we suggesting that every cheeseburger you eat is going to haunt your children and your children’s children to the seventh generation like some trans-fat-sodden biblical curse. We simply want to emphasize that the science of inheritance is undergoing a sea change. Parents’ actions can hide in their genes, molecular stowaways riding along unbeknownst to the chromosomes carrying them. We don’t yet understand every motive epigenetic influences have for climbing aboard, but we are aware of one particularly prominent cause: stress.
Chapter 9
The Neural Garden
Sophie lies awake in bed. Tonight sleep has been slow in coming. She mulls over the day’s events in her mind, wincing at each commitment she willfully piled onto her already overburdened schedule. At every request, absurd promises
