Meditations on Epigenesis

Strange beginnings to some thoughts about epigenesis. For those of you who aren’t sure what that means, it’s the part of biological development involving gradual differentiation of an unstructured embryo from genotype into phenotype (that is, from what is encoded in the genes to what actually appears as an organism). Much of our development is not so much directly determined by the genes, as by all sorts of influences about how the genes actually get expressed, many of which are environmental. This makes quite a hash of any and all questions about nature vs nurture. Even of the more sophisticated questions that take for granted that the relationship can never be additive, but must be at least multiplicative. If either of the terms is zero, you have a zero product. I was actually wondering whether you could, as in some kind of moral equation, have negative terms. If one term is, say, evil, don’t high numbers of the other term make it worse, like the evil genius? Or perhaps like the tragic flaw that leads to the demise and undercutting of heroic achievements.

Some of the epigenetic realities are really pretty profound, and pretty central to our humanity, like the homeobox gene that controls the expression of the genes governing the growth of the neural tube. These are pretty ancient genes, also responsible for things like the segmentation of insect bodies. In the embryogenesis of the neural tube, the “head” segment is, obviously, about the development of our brains. What if, in the growth of the head end, the genes controlling this segment were left “on” a bit longer? You get big-brained creatures, you know, like elephants, dolphins, and, oh yes, apes. I was actually a bit surprised to find that the mammalian but remarkably water-adapted creature, the hippopotamus, can neither swim nor float, but dances tiptoed across a river, holding its breath each time it goes under, and that it is more closely related to Cetaceans than to other land-based mammals. In homo sapiens there is also a peculiar hypertrophy of the frontal cortex, and especially of the most anterior prefrontal cortex, responsible for most of our higher cognitive functions -- which, uniquely, has input to the midbrain limbic system mostly responsible for our emotions, so we can be excited, or afraid of ideas as well as of more direct dangers. Who says we shouldn’t fear art?

One of my favorite epigenetic examples, and this is of an environmental influence on human development, is the role of a father-absent household on menarche in a developing pre-adolescent female. I could certainly spend pages qualifying this controversial example and, for my money it may actually turn out not to be exactly true. But it is a great illustrative example, even if it is not. Father-absent females are likely to experience menarche sooner, and be sexually active at a younger age. The just-so evolutionary story is that the girl gets the message that men don’t seem to commit very well to her mother, and, being like her mother, her best evolutionary strategy may be not to hold out for commitment, but to get the reproductive advantages of getting herself on the sexual marketplace while she is still rather more nubile. It’s not like she reasons through, decides this, and then starts her menstrual cycle by some effort of will. Evolution has figured this out for her, and just tunes her biological expression to the developmental realities of her particular domestic social environment.

The better known example of epigenesis is the more troubling one about the effects of early life trauma. Even if you are in utero, and your mother is in a more dangerous or stressful environment, your neurobiology is likely to be tuned for such an environment. We have talked before about the startle response. If you are tuned for a more dangerous or unpredictable environment, you are likely to startle more quickly to sudden changes. If the environment is more dangerous or unpredictable, this is certainly adaptive. But it may also be correlated with later political views in which you might favor social arrangements more conducive to your safety than to your freedom, like more restrictive immigration policies, stronger military capabilities outside, and stricter policing inside your community. In point of fact, there are long-term changes in sufferers of combat PTSD that involve similarly higher levels of neural responsiveness. There are even arguments that in a rapidly changing and unpredictable environment, ADHD may be more adaptive. If I’m on a patrol in the jungle, I’d want the guy with ADHD, who is hyper-responsive to anything, on point. We’ll live longer.

For any of those of you who know me (or who are getting to), it is interesting that children with mothers that have been through some stress during pregnancy are more likely to prefer more drama in their lives. My mother got whiplash when she was pregnant with me, which may have something to do with my having traveled farther and lived longer distances from home than either of my brothers, to say nothing about, I confess, having a bit more, um, “unrestricted sexuality.” Of course, that may have more to do with, say, having run full-bore into a brick wall at age 5, or getting hit over the right supraorbital cortex with a baseball bat at age 14. But then, such injuries are also consistent with being somewhat less risk-averse. Happily I am in pretty good shape, and I appear to have the right chemistry to live a long life, but my physician thinks he is more likely to live beyond 100. When I asked him why, he said “you are more of a risk-taker”-- the week after my first skydive.

So, what “strange beginnings”? We just celebrated my wife’s birthday, which my favorite aunt reminded me only last fall was also my long-deceased father’s birthday, though, of course, my wife is just 29 -- my mother once told me that women didn’t age past 29, and insisted that was her age until her stroke at around the millenium. That fact and that my birthday is also a 20th are the sorts of coincidences that seem to demand some greater significance, the same sorts of coincidences that get overplayed in stories of identical twins, separated at birth, and reunited well into adulthood. Like the Ohioan “Jim Twins,” who both chain-smoked the same cigarettes, bit their fingernails, had bad headaches, had garage workbenches, dogs named “Toy,” got married twice to women with the same names, and had sons they named “Jim.” I had a colleague once who surprised me at having the same birthday, and then told me that her husband’s was the same. What are the odds of that? Well, there are 365 days in a year, and a world population pushing 8 billion, so do the math, even with a US population of over 300 million, it’s not going to be that infrequent. So there is the birthday thing. That and twins. My two younger brothers are twins, hah, born in the “twin cities” of Minnesota, which houses the data of the Minnesota Study of Twins Reared Apart, to say nothing of the Minnesota Twins baseball team, go figure. But my brothers are as different as night and day. One got multiple letters in high-school sports, and the other, only because he was “most-improved” for three years in a row. One is a Chicago lawyer, the other a landscape architect in Dayton, Ohio. One has a son married in Ohio who now has three sons of his own, the other had three daughters, the eldest of whom just got married in South Africa. So, no, “womb-mates” aren’t normally expected to have any greater similarities than other siblings, aside from being in the same cohort. But my father had an identical twin. Back to Melvin and Myron in a bit.

I also just finished reading the fifth book in the “Girl with the Dragon Tattoo” Millenium series, this one called “The Girl Who Takes an Eye for an Eye,” wherein we learn that Lisbeth was a failed “apart” in a highly unethical set of studies of twins separated on purpose and placed in as different of homes as possible. Lisbeth is dizygotic (two eggs, not identical), but there is a subplot about two musically-inclined monozygotic twins. Leo is a gifted pianist, but ends up following his wealthy family into finance, whereas Dan is the one raised by an authoritarian single father against whom he rebels to follow a career playing jazz guitar. The author is pretty good about laying out Leo and Dan’s similarities and differences. The wealthier Leo is, as one might expect, better coiffed and more likely to wear expensive tailored suits, nevertheless the one eking out a career as a musician (what do you call a musician without a girlfriend? -- homeless), after a youthful period with long hair and an earring, trying different drugs and love affairs, started to wear gray suits by about age 35, and could be mistaken for an office worker. Leo's suits also tended to be gray. Dan’s life had been changed by hearing the music of Django Reinhardt, and often played “Minor Swing” and “Nuages.” But when he soloed on “Stella by Starlight” at a club full of finance people, instead of following the two-five-one progression, he played entirely outside the Bb key of the piece. Both men played the same major triad arpeggios, ending a half note up from the keynote. They used the older diminished chords, often landing on the sixth note in the Dorian scale. A woman in the crowd mistakes him for Leo, recognizing some of the same harmonies Leo used on his piano, and wonders when he switched to guitar, finding his playing “magical” and “insanely good.” Of course Dan has had more years as a professional musician, but both prodigies lacked initiative, were prone to doubt and depression, loners with an ambivalent attitude toward their solitude. Still, the wonder and excitement of finding a previously unknown twin is captured well in The Girl Who Takes an Eye for an Eye. This is even true despite their being “mirror” twins, when the egg splits into two a little later. Hence, when Dan “fills in” for Leo, a shift in handedness is one of the clues. My Dad and my uncle were also mirror twins, interesting since most of us imagine our appearance by what is actually the reverse image we see in the mirror -- why looking at a friend in a mirror always makes them look a little distorted, as the normal asymmetries are reversed.

Now, who of us hasn’t occasionally wondered about having a doppelganger out there somewhere? I could’ve sworn when I met the husband of my ten-years’ lost first love that he looked like me. OK, except a little handsomer, taller, and more confident. But I do remember how much I was surprised that the baritone singing in front of us in the church of my youth had my same name, and I know there is a musician named “John Teske,” as well as a famous photographer, so it’s hardly unique. I was once told that there were as many Teskes in the Hamburg phone book as there are Smiths anywhere in the US, and “John” was a pretty ubiquitous boy name for my cohort. It always annoyed me when people talked about having a clone to reproduce their identity, when a clone would be less alike than an “identical twin” being raised in a different era. Now, while even things like religiosity may have relatively high heritability, most traits are polygenetic in any case, which is why heritability ratios on any number of traits tend to be much higher in identical twins than the mere doubling of ratios one would expect over dizygotic twins or mere siblings. Moreover, there are numerous other genetic influences, including the evocative ones of the patterns of care a child elicits, the passive ones of the environment parents provide (like the presence of books in my children’s world), or the active ones of niche-choice and even niche-creation that are likely to intensify as we develop (Sandra Scarr). This is probably why identical twins raised apart can have so many “coincidental” similarities. Most identical twins raised together, especially in an individualistic culture, are encouraged to differentiate, and may seem the most different just before they leave home and pursue separate lives. In an image of my father’s family just before the older boys left to fight in WWII, Myron and Melvin couldn’t look more different. My father, Myron “Mike” Teske, is on the left, looking softer and more thoughtful, separated from his “mirror twin” Melvin by their older brother Alan, Mel squared off and standing tall like Alan, looking more the pair.

Identical twins are still separate individuals, with separate consciousness, separate identities, formed from differences in experience that can accumulate and magnify over a life-span, but can start with different positioning in the womb. It always gave me a unique perspective, when teaching a generation of undergraduate psychology students about genetics and the environment, the “nature-nurture” question, that my father died young, at the age of 67, of a sudden heart-attack, and his identical twin outlived him by almost 20 years, succumbing to a long battle with Alzheimer’s. My Dad was not only the second born, but the “lefty” which in those days meant he was subjected to a number of failed efforts to get him to write with the other hand. He had rheumatic fever as a child, and Mel did not, leaving Mike with the stenotic heart valve that would finally stick, stopping his heart, a sudden and unexpected death at 67. Mike was also born with a spinal curvature, suffering after being declared 4F, unfit for duty, until the need for troops meant that any able-bodied young man would be taken. Mel served in the artillery, and came back from the war a little deaf, and with some other issues that would leave him with ulcers.

Mike was a grunt, a PFC who was a replacement at the Battle of the Bulge, where being “Cherry” he was not expected to live long. Nineteen years old, lugging his 8-pound Garand rifle through the coldest winter in Belgium in 100 years, he was part of the three-man radio team in his platoon, which included his lieutenant, the radioman, and my dad, the lieutenant’s de facto bodyguard. Taking a break at a Belgian farmhouse, the lieutenant told them to go inside to warm up and get a cup of coffee. So my dad was inside when the top of the lieutenant’s head was blown off by a sniper. My dad told me the only use he ever had for a boot-knife his father probably gave him in some Audie Murphy trench-war fantasy, was when friendly fire landing in their own trenches meant there “wasn’t a dry pair of pants in the trench” and he needed it to cut off his own beshitted pants. After weeks of deadly stress, the platoon members fingernails started turning yellow, a sign of the jaundice from their livers shutting down. They would have soon been dead had they not been taken off the line and sent to a hospital in Paris to recover. I have no doubt that my father was traumatized by the war, though it took him until middle age before his depression finally broke him down. During my junior year in college, he got twelve treatments of electro-convulsive shock. Mel had become an insurance lawyer, staying closer to my Milwaukee-Deutsch forebears. My father had become a Lutheran Campus Minister, first at Wisconsin and then at Purdue University, organizing "hunger hikes" fueled by his memories of Belgian kids digging food out of GI garbage, and speaking out against the war in Vietnam. The ECTs left him with some memory problems and, I always thought, de-cored him. Offered only a rural parish after his depressive episode, in the era when a VP candidate would be eliminated for having “depression in remission,” he worked as a janitor, and then for the Purdue mail service, becoming a “mail-truck theologian,” and a fly in the ointment of the university parish. But his funeral at that church was standing-room only, and few moments passed when one couldn’t hear an audible sob somewhere. After seeing grandpa’s open casket in the narthex of the church, my then-young children were surprised to see him apparently risen from the dead when my Uncle Mel arrived late at the wake. By this time, they seemed so different to me, but to my children, who may never have seen Mel before, they were identical.

So like the Dioscuri, the warrior twins Castor and Polydeuces in classical mythology, the twins were different. Castor was mortal, Polydeuces another immortal choosing not to be parted from one he loved. About Thomas Didemus, Thomas the twin, putatively author of the gnostic gospel of Thomas, the sayings of Jesus, who knows? I think there is actually a surprising number of infants who started out with a twin, consumed or absorbed in the womb. But the identities formed over a lifetime are far from identical. But I also have to wonder. I am probably the adult child of a PTSD sufferer. Though that diagnosis was a product of the Vietnam war, something like 60% of the hospitalised veterans of WWII were “psychiatric casualties.” Clinical Psychology as we know it in this era probably began as a need to fulfill mental health roles for which the psychiatric ranks were inadequate. I know my father was traumatized by the war, the stress that brought out the diathesis he may have shared with Mel. But what about the effect on the next generation?

My “bible” of child development, Melvin Konner’s The Evolution of Childhood makes us take the idea of a life-span seriously, to understand the human person not synchronically, as an object existing at a particular moment, but diachronically as consisting of a certain kind of life-span, that what evolves is not organisms but life-spans. Konner also divides his 900-page tome into four separate sections. One is on “evolution” and the phylogenetic emergence of childhood. He also separates socialization, the evolving social context of childhood, looking at its relationships to socialization in related species, from enculturation, the transmission and evolution of culture, which is what makes us so different from other animals, and makes human history important to understanding childhood development. But there is also one whole section on maturation, about “how neural and endocrine systems guide the paths of development called for by natural selection.” This is epigenesis.

It was a recent article in the New York Review of Books by Israel Rosenfield and Edward Ziff on “Epigenetics: The Evolution Revolution,” which discussed not only the sort of epigenetic influences I have already raised, but suggests a more disturbing possibility. The Epigenetic Revolution and The Deepest Well, the latter about childhood trauma, are recommended sources. Researcher suggested in 1975 that methylation, a chemical modification of DNA that has a role in controlling gene expression -- hence epigenetic -- can not only be induced by environmental influences, but can itself be inherited. Extreme childhood stress, like abuse, trauma, famine, and even ethnic prejudice, can produce long-term effects on genetic expression. Preventing the expression of certain genes can be a hidden cause of depression, anxiety, or paranoia.

So far, OK. But could this environmentally induced alteration in the expression of certain genes be passed on to children who never themselves experienced the stressors that caused a parent’s depression or ill-health? We understand that childhood trauma, like a parent’s death, a divorce, violence or abuse for example, can result in health problems in adulthood, like heart disease, cancer, mood and dietary disorders, substance abuse, learning deficits, and sleep disorders. Normally our bodies release a hormone, a glucocorticoid, which prepares us for challenges by adjusting heart rate, energy production, and brain function, which then binds to the glucocorticoid receptor protein to shut off its own production. But for people who have experienced childhood stress, the gene for the receptor is inactive, so the hormone keeps being released and the stress response continues. What this means is that the body cannot regulate its own stress response. DNA methylation produces the barrier. The long term consequences: chronic inflammation, diabetes, heart disease, obesity, schizophrenia, and major depressive disorder. Yes, this can be passed to offspring “who have not themselves experienced” the stressor but may have similar epigenetic sequelae, probably via the mother’s transmission of glucocorticosteroids through the placenta. This produces greater risk of preterm delivery, birth weight and miscarriage, but also problems of temperament, attention and mental development in infancy, hyperactivity and emotional problems in childhood, and schizophrenia and depression in adulthood.

So, OK, my father suffered from depression and, to some extent I have the same depressive diathesis, also shared by his twin brother but, lacking the necessary stressors not made manifest. I’m in a similar genetic situation as my Uncle Mel. Clearly any trauma my mother experienced during pregnancy could also result in my own stress-response malfunctions. And, yes, the evocative, passive, and active genetic effects of having my PTSD symptomatic father around, could also contribute. But no, that does not mean, that in any Lamarkian sense, the epigenetic alterations in my father which resulted from his wartime trauma, which I did not experience, could be directly and biologically visited upon me. So the sins of the father, actual things he did or experienced in his lifetime, are not, genetically or epigenetically, visited upon his son. This doesn’t mean the apple falls far from the tree.