Intergenerational epigenetic inheritance ("trauma") being Fake

Alden Whitfeld on X

Intergenerational epigenetic inheritance, especially on “trauma”, is a meme. First of all, almost the entirety of its effects are erased during early development in the germ line [1][2][3]. Second, humans don’t even have a stable mechanism to transmit such effects successively across generations in the first place, as noted here [4]: "A simple illustration of genuine intergenerational transmission that requires no imaginative gymnastics would be famine which induces stress on the pregnant mother, her female fetus and the female fetus’s own eggs, where all exhibit epigenetic responses due to a simultaneous and singular external shock. The longest possible chain of generational impacts of this event would reach to the children of a female fetus in utero at the time of the external stressor (the third generation). And if the fetus were male, the effect could not persist beyond him in the second generation, because males continuously produce new sperm cells throughout their lifetime; no mechanism exists for them to transmit the famine-induced changes. Any posited intergenerational “transmission” cannot then be literal transmission, but at most correlation due to the same shock contemporaneously impacting parent and offspring (and if the fetus is female, egg cells). Multiple generations, yes, but only in the way that multiple generations living through a catastrophic earthquake carry its scars in various forms for the rest of their lives. In contrast, under transgenerational transmission, the stress marks induced by the external shock are thought to be copied generation after generation so that the effect persists much longer. If transgenerational transmission does occur in humans, you might expect descendants of the Armenian genocide to be biologically impacted by that event more than a century on. But we don’t even need to take this line of hopeful speculation seriously, because epigenetic transmission across multiple generations almost certainly does not occur in humans at all. Mammals generally would be unlikely to exhibit transgenerational epigenetic transmission due to the simple facts of our reproductive biology. Though transgenerational epigenetic transmission grabs the public spotlight, it accounts for far less than 1% of the research published that can be classed as “epigenetics” (and this is on any species, least of all humans!). Instead, for humans and all complex organisms, epigenetics remains both incredibly important and ubiquitous, but solely as a cellular and developmental phenomenon. To understand epigenetics in its full power, you talk to a molecular biologist that works with DNA, not a therapist probing the pain points of your family history." But how is epigenetic inheritance even established empirically? The actual state of the research is quite abysmal. Practically all of the commonly cited studies on transgenerational epigenetic inheritance of trauma that make it to pop-sci commentary are based on extremely small samples or highly unreliable and imprecise methods. In fact, their own results do not provide even weak evidence for the claims of "inherited trauma" [5]. To quote Steven Pinker from his afterword to his book The Blank Slate: The Modern Denial of Human Nature [6]: "that some epigenetic markers attached to the DNA strand as a result of environmental signals (generally stressors such as starvation or maternal neglect) can be passed from mother to offspring. These intergenerational effects on gene expression are sometimes misunderstood as Lamarckian, but they’re not, because they don’t change the DNA sequence, are reversed after one or two generations, are themselves under the control of the genes, and probably represent a Darwinian adaptation by which organisms prepare their offspring for stressful conditions that persist on the order of a generation. (It’s also possible that they are merely a form of temporary damage.) Moreover, most of the transgenerational epigenetic effects have been demonstrated in rodents, who reproduce every few months; the extrapolations to long-lived humans are in most instances conjectural or based on unreliably small samples. Biologists are starting to express their exasperation with the use of epigenetics as “the currently fashionable response to any question to which you do not know the answer,” as the epidemiologist George Davey Smith (2011) has put it. Other deflations of the epigenetics bubble may be found in Coyne, 2015; Heard & Martienssen, 2014; Juengst, Fishman, McGowan, & Settersten, 2014; Moffitt & Beckley, 2015; and Haig, 2007." Indeed, what is often taken as an epigenetic effect in these rat studies often isn't even one. An example can be seen from "the well-known observation that stressed female rats have stressed offspring. That is because stress reduces maternal care of the newborns, which is itself stressful and which sets up long-term changes in expression of the glucocorticoid receptor. But this is a behavioural transmission: mom’s behaviour affects offspring’s behaviour – repeat. This is not an example of epigenetic inheritance via the gametes, which is what has been proposed as a possibly important mechanism" [7]. But wait, it gets even worse. Because as it turns out, variation in gene expression and DNA methylation themselves are in fact genetically mediated [8]. Moreover, epigenetic effects also vary unsystematically and have generally little predictive validity [9]. In reality, the totality of the evidence indicates that epigenetic effects are not a significant source of variation in humans, as noted by Davey Smith: "This dismissal of heritability might feel like good news to epidemiologists—it gives more room for the environmentally modifiable risk processes we want to identify in order to leverage public health improvement—but is, I think, short-sighted. Most importantly, it is empirically poorly founded. Whilst it is possible to generate a list of potential fallacies in the estimation of heritability—such as challenging the assumption that monozygotic and dizygotic twins have equally similar environments—these apply to only one method of estimation (classical twin studies), and different designs, such as studies of twins reared apart, extended twin-family studies, adoption studies (including quasi-randomized adoption) and extended pedigrees generally yield similar estimates of heritability. All of these designs are susceptible to bias, but they are different biases, and it is unlikely that they would all distort the findings in the same direction and to the same extent.17,29 Heritabilities for various traits are generally similar in animals studied in captivity and in the wild,30 something difficult to envisage if they were generated by artefact." Davey Smith also goes on to review several different lines of evidence for transgenerational epigenetic inheritance and highlights the problems with them, concluding that "The conclusion from over 100 years of research must be that epigenetic inheritance is not a major contributor to phenotypic resemblance across generations, yet strangely—and perhaps because of the unexceptional nature of the findings—this vast literature has, in some circles, been forgotten. Instead, occasional examples of phenotypically consistent epigenetic inheritance relating to a particular phenotype in a particular organism are given considerable attention, with the implication that they represent a general phenomenon" [10]. Just as one example of how ridiculous the commentary on intergenerational epigenetic inheritance is, take a 2017 article from Culture Whiz titled “Genetic Determinism Debunked”. Aside from the article basically being one long rant hyping up epigenetic effects, the only important part of the article is when its writer at least had the honesty to admit that epigenetic effects “can also be very readily reversed”, citing the SAME study he used to originally hype up epigenetic effects (do these guys have any self-awareness at all?) [11]. You may think you're very clever because you have the ability to pull up the first link you see on Google about "inherited trauma", but I am here to tell you that researchers who actually know what they're doing are aware that it's bogus. The fact that you personally decide to outsource your thoughts doesn't change this.