Human Diversity
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Taking its results overall, NEAD was successful in identifying nonshared environmental influences. Only a few of these seemed to make a difference psychologically, however. Causation also tended to go in the “wrong” direction: The genetics of the child was often what made the twins’ environment “nonshared”—for example, as in the case of a child with a genetic personality disorder that prompted the parents to treat the affected twin differently from the unaffected twin.
Subsequently, other research documented another unwelcome aspect of the nonshared environment: One of the securely known features of MZ twins is that their differences in psychological traits cannot be genetic (because they share the same genes); they cannot be caused by differences in the shared environment (by definition); and therefore such psychological differences must be due to the nonshared environment. But it has been found that those differences are not stable over time. Cognitive differences last no more than a few years and personality differences change even more quickly. No identical twin differences are stable over many years.55 The necessary implication: The nonshared environmental factors are not stable, but more like random noise. Writing in 2018, Plomin reflected on what had been learned since he described the nonshared environment in 1987:
Rather than accepting this gloomy prospect at the outset, it made more sense scientifically to look for possible systematic sources of non-shared environmental effects. However, after thirty years of searching unsuccessfully for systematic non-shared environmental influences, it’s time to accept the gloomy prospect. Non-shared environmental influences are unsystematic, idiosyncratic, serendipitous events without lasting effects.56
Is it possible that aspects of the nonshared environment can be affected by outside interventions? The prospects are, to borrow a word, gloomy.
“But You’re Ignoring Epigenetics!”
Raise the topic of genes’ role in affecting human behavior, and chances are good that someone is going to tell you that you’re hopelessly behind the times. Epigenetics has proved that alterations in the environment can change our genes, and therefore traditional beliefs about inborn characteristics are outdated and irrelevant.
It’s no surprise that this view is so widespread. Respectable media have been reporting it for years. Time magazine explained “Why Your DNA Isn’t Your Destiny” back in 2010, with the subtitle “The new field of epigenetics is showing how your environment and your choices can influence your genetic code—and that of your kids.”57 In 2013, Discover magazine told us that “the genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch: Shake it hard enough, and you can wipe clean the family curse.”58 The New York Review of Books weighed in with “Epigenetics: The Evolution Revolution” in its issue of June 7, 2018. Authors Israel Rosenfield and Edward Ziff reported, “Epigenetics has also made clear that the stress caused by war, prejudice, poverty, and other forms of childhood adversity may have consequences both for the persons affected and for their future—unborn—children, not only for social and economic reasons but also for biological ones.”59
It’s not just the big events like war that can change our brains. Jogging can do it too. Here’s Tara Swart, holder of a PhD in neuropharmacology from King’s College London, writing in Forbes:
The new and evolving science [of epigenetics] tells us that our gene expression is malleable, influenced by external stressors and lifestyle choices, from running outside to who you have your coffee break with. Rather than having a set genetic blueprint, epigenetics demonstrates that although our genes themselves are fixed, our genetic expression, much of which is heritable, is also interconnected with a wide range of environmental factors.60
With rare exceptions, the mainstream media’s reporting on the science behind epigenetics bears little resemblance to what’s actually been discovered.
The Basics
Your personal double helix of DNA resides in the nucleus of a cell. The rest of the cell contains the proteins that enable it to perform its particular function, whether it be a cell in a biceps or the brain. For a cell to do that, somehow the small number of relevant genes in the DNA producing those proteins for that cell type must be identified and their information transcribed. Then the transcription must be transferred to the ribosome, the place in the cell where proteins are synthesized.
The steps in the process of getting the information to the ribosome are all part of gene regulation, also called regulation of gene expression—turning genes off or on and turning them up or down. Some of them involve a class of chemical modifications to DNA or to components of the “packaging” of DNA (chromatin) that has led to what is now called epigenetics.
The word epigenesis was first used in 1651 by William Harvey to describe the developmental process that allows the homogeneous fertilized egg to become a complex organism. In 1942, embryologist Conrad Waddington coined epigenetics, which he defined as the “whole complex of developmental processes,” portraying an “epigenetic landscape” of branching pathways that a cell might take.61
In 1958, just a few years after the discovery of the structure of DNA, microbiologist David Nanney recast Waddington’s definition. Nanney described two types of cellular control systems. One consisted of “genetics systems” that are involved in transcription. The other consisted of “epigenetic systems” that were auxiliary mechanisms for determining whether expression occurred, and if so, its intensity.62 Nanney’s article also drew attention to what would become a major aspect of epigenetics: “persistent homeostasis,” referring to cellular memory that survives cell division.63
What caused “persistent homeostasis”? Collapsing decades of research into a few sentences and simplifying, the answer turned out to be epigenetic marks of two kinds: those caused by DNA methylation and those caused by histone modifications. I will concentrate on DNA methylation, which has been more commonly studied, and ignore histone genetic marks in this short description.
THE DNA DOESN’T CHANGE
No one claims that the DNA code is modified by environmental events. All the scientific claims involving epigenetics, correct and incorrect, are about changes in gene expression, not changes in DNA.
For DNA methylation, the genetic mark can be thought of as a speck of a chemical in the methyl group64 deposited onto a gene. The most common effect of methylation is to turn off the gene—to suppress its expression by making it less accessible to the transcription machinery—but in some circumstances it can turn on genes or modulate their intensity.65
The task of methylating the genome begins early in life. At conception, a fertilized egg contains not only DNA inherited from the parents but also the parents’ methylation patterns. About a week after conception, almost all of those patterns are erased and almost all of the genome is methylated de novo. This new genome-wide methylation pattern paves the way for cell specialization by repressing DNA sequences that aren’t supposed to be expressed in a given cell. During pregnancy, methylation and demethylation continue at specific stages of the embryo’s development in a programmed sequence until the tissue is fully developed, whereupon it has generated a template that is extremely stable lifelong.
Extremely stable, but not completely so. Abnormal methylation events do occur during the lifespan and have been implicated in various diseases, including some cancers. This brings us to the heart of the excitement over epigenetics: the evidence that changes in methylation can be induced by environmental events.
In the breathless accounts of the epigenetics revolution, a commonplace truth often gets lost: Environmental events routinely change gene expression. If you break a bone in your ankle, expressions of genes in that bone are going to change so that the bone may heal. If you run a mile, a variety of changes in gene expression will have taken place in your respiratory system. That the environment interacts with genes to change the phenotype temporarily is not news. It happens all the time.
The distinctiveness of epigenetic change lies in the cellular memory of methylation
that survives cell duplication. Suppose that a negative environmental event early in childhood not only caused temporary changes in gene expression (as in a broken ankle), but changed the methylation patterns, thereby causing permanent genetic changes that damage the phenotype. Suppose that a subsequent positive environmental event could demethylate and thereby reactivate the genes that had been turned off by the negative event. Suppose—and this was the most exciting possibility of all—that cellular memory not only survived during the lifetime of the person who had experienced these environmentally induced genetic changes, but could be passed on to offspring.
That’s where the hype over epigenetics originated and why it has been so attractive to the media. Epigenetics seems to promise release from genetic determinism. It seems to offer new explanations for phenotypic differences and new possibilities for remediation. At the extremes, it seems to offer hope for greater equality of capabilities and outcomes across groups.
As these potential extensions of findings about gene expression sank in during the 2000s, the use of the term epigenetics expanded to include all forms of transmission of the phenotype by mechanisms that did not involve changes in the DNA sequence—in other words, to expand beyond Nanney’s emphasis on cellular memory and instead treat the larger realm of transmission of the phenotype through RNA and transcription factors as part of epigenetics.66 For John Greally, director of the Center for Epigenomics at the Albert Einstein College of Medicine, this is too broad a definition, conflating changes in transcription regulatory effects with cellular memory. This has created pervasive problems of interpretation—among other reasons because a change in DNA methylation can be an effect instead of a cause.67 But for better or worse, the broad interpretation of epigenetics has taken hold and a correspondingly broad research agenda based on it has been pursued for two decades. What has been found?
The Claims of the Advocates
The first significant claims for epigenetic change were tailor-made to feed into both the optimism and the media excitement: They dealt with the effects of maternal love in infancy. The article “Epigenetic Programming by Maternal Behavior,” published in 2004 (first author was Ian Weaver), reported that rat pups who received high levels of arched-back nursing plus pup licking and grooming had differences in DNA methylation of a specific glucocorticoid receptor in the hippocampus compared to pups who received low levels of such nurturing.68 That particular receptor has been the focus of attention because it regulates genes known to affect early development, especially including the response to stress.
Media accounts immediately drew the obvious implication of the Weaver study’s finding: If these effects occurred in rat pups, perhaps human children who are deprived of such maternal care are permanently less able to cope with stress and more vulnerable to psychological disorders for genetic reasons. The authors further concluded that the effects on methylation were reversed with cross-fostering. “Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.”69 The media also fastened on this implication: Something can be done to undo the genetic damage experienced by children who were deprived in infancy.
Since 2004, a flood of articles in technical journals has pursued the possibilities that the Weaver study suggested. The ones that have received the most media attention focus on “natural experiments” in the form of the Dutch famine of 1944–45, the Chinese famine of 1959–61, and the children of Holocaust survivors. Most of these studies are correlational. For example, studies have documented significant increases in the incidence of schizophrenia among children born in both the Dutch and Chinese families.70
In the case of the Dutch famine, a team of Dutch scholars compared methylation 60 years later of people who had been in utero during the worst of the famine with siblings who were born before or after the famine. Their conclusion:
In summary, using a systematic genome-wide approach, we show that DNAm [DNA methylation] at specific CpGs [cytosine-phosphate-guanine dinucleotides] mediates a considerable proportion of the associations between prenatal famine exposure and later-life adiposity and serum TG levels. Our data are consistent with the hypothesis that the associations between exposure to an adverse environment during early development and health outcomes in adulthood are mediated by epigenetic factors. The specific causal mechanism awaits elucidation.71
In other words, what happened to the children in utero probably affected DNA methylation in ways similar to those of laboratory studies, but the data didn’t permit the authors to determine whether it was the stress on the mother or the stress on the fetus (or both) that caused those effects on methylation, nor could they tell whether the changes were due to changes in DNA sequence variants or other factors.
In 2016, an article on Holocaust survivors and their children got widespread media attention in the Guardian, New York Times, and Scientific American. Based on 32 Holocaust survivors and 22 of their adult offspring, the authors (first author was Rachel Yehuda) reported, “This is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects.”72 The key adjective for the parental trauma was preconception. Unlike the study of methylation in the children of the Dutch famine, the Holocaust survivor study claimed to have evidence of transgenerational epigenetic inheritance.
As I write, two systematic reviews of the epigenetics literature have been published. The first, published in 2016, was written by psychiatrist Gustavo Turecki and neurobiologist Michael Meaney. Their review of the literature identified 430 articles, of which 40 met the authors’ criteria for inclusion.73 The other systematic review, published in 2018, was prepared by a team supervised by developmental psychologist Wendy Kliewer. The authors limited their review to studies of infants, using 20 out of 510 unique articles that their literature search had identified.
Neither review found support for epigenetic effects resembling the portrayal of epigenetics in the media. Neither discussed transgenerational epigenetic change. You may check out this characterization of the results for yourself. All of the major findings are presented in the note.[74]
The Responses of the Critics
A familiar story in the history of science is that a paradigm-breaking discovery—the heliocentric solar system, quantum mechanics—is made by Young Turks, resisted by the older generation of scientists, and finally wins acceptance as the geezers die off (“Science advances one funeral at a time”).75 But that’s not how the epigenetics debate is being conducted within the profession. Epigeneticists who are still young themselves and doing cutting-edge work see their discipline as the victim of a hijacking. In their view, too many epigenetics enthusiasts are reaching conclusions and publishing them without understanding the science that already exists. For John Greally, the Yehuda study of Holocaust survivors “is pretty typical of all epigenetics studies today for being uninterpretable.”76 Geneticist Graham Coop had a Twitter response to the New York Review of Books article that began, “Utter nonsense.” And they have allies in the older generation—the week that the New York Review of Books article came out, evolutionary biologist Jerry Coyne’s blog began with “Another lousy article on epigenetics.”
For those who want to pursue the debate, I can point you to an exchange that gives you an overview of the issues and references many of the key sources. The protagonists are neuroscientist Kevin Mitchell and Jill Escher, a well-known advocate for autistic children.
Mitchell’s case against the popularized version of epigenetics began with two long scholarly appraisals of the data posted on his blog, Wiring the Brain, in January 2013.77 In May 2018 he returned to the subject in the wake of the Yehuda study of Holocaust victims. He was blunt. “You could be charitable and say the evidence is weak, circumstantial, observational, and correlative, and that it warrants circumspection and careful interpre
tation (and further research, of course!). I would go further and say that nothing in any of those papers rises to the level of what should properly be called a finding. There’s no there there.”78
A month later, Jill Escher responded on her blog, Germline Exposures, with a list of 49 references documenting her allegation that Mitchell cherry-picked studies to make his case and ignored abundant evidence of epigenetic inheritance in mammals. She was as blunt as Mitchell:
Sloppy overstatement and dogmatism from the Ivory Tower, such as Mitchell’s blog post, can breed complacency precisely at a time when we should be deeply alarmed about the intergenerational effects of past and current exposures. It should be clear to all of us by now that molecular insults to the germline can influence disease, behavior or physiology of offspring, perhaps in ways that are staggeringly important for public health. While healthy skepticism is always welcome, research does not progress by allowing outspoken academicians to distort the state of the science, unchallenged.79
Four days later, Mitchell responded to Escher with another detailed methodological critique of the epigenetics literature.80
If you’re wondering how an outsider is to form an opinion, I sympathize. Of the many complex topics in this book, I found epigenetics to be the most impenetrable for an amateur. I come away from the literature thinking of the controversy in terms of two broad issues.