A forthcoming paper titled “Holocaust exposure induced intergenerational effects on FKBP5 methylation” by Rachel Yehuda and many others is sparking considerable debate about epigenetics, mostly—according to my Twitter feed, at least—as critiques of this paper. I do not have access to the Yehuda paper, and so I am unable to discuss the appropriateness of its methods or the validity of its conclusions, but luckily that is not what I find most interesting about the responses evoked by this paper. Instead, given my focus on the politics and ethics of epigenetics, what I find of particular interest is a blindspot regarding the ethical implications of conventional evolutionary theory revealed by some of these critiques of this paper.
Epigenetic inheritance and the Holocaust
The takeaway of the Yehuda paper, according to the authors, is that they have been able to demonstrate for the first time the “transmission of pre-conception parental trauma to child associated with epigenetic changes in both generations, providing a potential insight into how severe psychological trauma can have intergenerational effects.”
The trauma in question is direct experience with the Holocaust, and the authors claim to show that the Holocaust survivors in their sample demonstrated significantly more methylation at a specific DNA base in the gene compared to controls, and that the offspring of these survivors showed significantly less methylation at that same site than control offspring. The gene in question is the FKBP5 gene, which has been associated with depression and stress responses, and a previous paper by Torsten Klengel et al. (2013) has shown that traumatized individuals show decreased methylation at this site. Therefore, the causal chain suggested by Yehuda et al. is that the experiences with the Holocaust of one generation increased the methylation at this gene, which resulted in the decreased methylation at this site in their offspring who now exhibit the methylation patterns of being exposed to trauma without having been exposed to the original trauma of the Holocaust.
Epigenetics and the ‘adaptation’ blindspot
So why has this paper attracted so much criticism? And what is the blindspot?
On the one hand, there are a number of methodological and interpretive issues with the paper which are already addressed in other critiques. That being said, most of these issues seem like science-as-usual which can—and should—be addressed through improved experimental design and replication. One particularly relevant critique in this regard, titled “Over-interpreted epigenetics study of the week,” is by John Greally from the Center for Epigenomics at the Albert Einstein College of Medicine. As an epigeneticist, Greally clearly does not have an issue with epigenetics or epigenetic inheritance per se; rather, his concerns are primarily with the methods and the interpretation of the results of the Yehuda et al. paper. Thus, these kinds of critiques, which can be very pointed, criticize but do not call into question the core concepts behind the Yehuda paper.
However, other critiques of this paper use these methodological and interpretive issues as a platform from which to dispute the validity and the value of the concept of epigenetic inheritance itself. These are the kinds of critiques of epigenetics and epigenetic inheritance which reveal the critical blindspot which originally prompted this post.
The best example of this blindspot is found in the critique of the Yehuda paper by the well-known evolutionary biologist Jerry Coyne. While Coyne’s extensive list of critiques of Yehuda et al. mirror those of Greally, Coyne continually couches these critiques in the context of asserting the inutility of epigenetic inheritance for adaptation. For example, even as Coyne concedes that “while environmental epigenetic modification of genes is known to exist, and even to be passed on for one or two more generations,” he qualifies this admission with the assertion that this kind of modification is not common, and “is not known to be the basis of any adaptations that have evolved in organisms.” In fact, Coyne continues, epigenetic modification are excluded “in principle” from being a factor in adaptive evolution. “While this is still a form of inheritance,” Coyne writes, “it’s not one that’s especially reliable given the vagaries of physiology.” What would make epigenetic modification more reliable, and therefore more worthy of study according to Coyne, is if they were proven to be directly transmitted via germ cells. However, Coyne concludes, “that doesn’t appear to be the case in this study.”
This lack of contribution of epigenetic modification to adaptation appears to be for Coyne the sine qua non of the validity of a concept: A biogenetic process is useful to the extent that it can be identified as contributing to evolutionary adaptation; to the extent it does not contribute to adaptation, it is not useful. To wit, even while admitting that “the authors are not arguing that this kind of inheritance plays a role in evolution,” Coyne still uses his critiques of their paper to discount the value of epigenetic inheritance as a concept worth researching because it does not play a role in evolution.
Epigenetics isn’t ‘Adaptive’? So What
So what? Even allowing for the sake of argument that these epigenetic modifications are not stable enough to eventually cause changes in DNA sequence [which I am not conceding, as a number of papers have suggested different ways these epigenetic modifications can prepare the way for eventual changes in DNA ], this Coyne-ian standard overlooks or disregards the mounting evidence that the environment is affecting gene expression in significant ways—perhaps not significant on a geological timescale as to change gene sequences, but significant on a human scale not only today but for our foreseeable future.
In other words, the political and ethical relevance of epigenetics does not depend on whether these modifications are ‘adaptive’ in the sense of modifying the genetic sequence (which is itself a very specific and unique definition of adaptation). If there are factors in the environment which affect gene expression through epigenetic modifications to manifest as positive or negative health outcomes in actual people, by almost any ethical standard these factors are or should be investigated to the fullest extent possible. To blithely dismiss the relevance of such processes, especially in the face of mounting empirical evidence, because they—theoretically—do not produce changes in DNA sequence seems akin to denials of global climate change or refusal to vaccinate based on political ideology or religious conviction.
Epigenetics and evolution
I can imagine a reasonable response from Coyne and other similarly-minded people that he/they are just speaking about epigenetics in regards to evolution in particular, whence the emphasis on genetic adaptation, and that of course epigenetics is valid and worthwhile in these other contexts. Even so, though, I would suggest that the gene-centric focus on evolution still has a blindspot about epigenetics, with significant repercussions for human well-being and values.
As Coyne points out in his critique of the Yehuda paper, even epigenetics have a genetic basis. According to Coyne’s own logic, then, this epigenetic responsiveness to the environment would only have evolved because it conferred actual adaptive benefits.The adaptiveness from the intergenerational transmission of information about the environment of parents to their offspring—however transitory—is not only easy to imagine but also the only reason these epigenetic mechanisms would have evolved in the first place. Therefore, to dismiss or discount the importance of epigenetics in evolution is a curious position for an evolutionist to take, and really only makes sense in the context of an almost religious focus on gene sequence as the only relevant parameter.
Epigenetics, evolution and ethics
However, the acknowledgement of an important role for epigenetics in evolution introduces significant ethical challenges to the detached focus on long-term genetic adaptation characteristic of conventional evolutionary studies. When the environment is relatively static, epigenetic responsiveness is likely not as much of a factor in evolution, nor that much of an ethical concern, functioning more as a temporary adjustment to ongoing conditions. But what if the environment changes in such a way and with such rapidity that what would otherwise be normal epigenetic adaptation manifests as potentially maladaptive phenotypes, which have an effect not only on the quality of life in the present and near-future but therefore also (potentially) in the long-run as well?
This is, I believe, the current state we find ourselves in, in which our environment has changed so rapidly and in such specific ways that these once beneficial epigenetic modifications are now resulting in uniquely maladaptive phenotypes. For example, industrial scale chemistry, the Plastic Revolution, and other accoutrement of our contemporary era, which have emerged only within the past hundred years or so, have introduced specific chemicals into our environments which interact with our genes via these epigenetic mechanisms in particularly pernicious ways. To assert that these mechanisms lack relevance or value because of their theoretical lack of effect on geological-scale processes smacks of either wanton disregard or sincere but myopic ideology.
Again, this is not to uncritically defend the Yehuda et al. paper which originally prompted this post, or to excuse any shortcoming of any other research in epigenetics. Methodological and interpretive flaws in any of these studies should be recognized and mitigated as much as possible, but this is just science. Rather, I hope I’ve been able to show that theoretical assumptions—such as an almost religious emphasis on genetic adaptation as the ultimate standard of value—have meaningful implications for our politics and our ethics beyond ‘just’ the science.
Sometimes the lines between science and values are very clear. Epigenetics muddies these boundaries to an unprecedented extent. The increasing weight of empirical evidence from legitimate research in epigenetics shows that we are much more closely connected with our immediate environments than we’ve previously assumed in ways which would seemingly also affect our evolutionary fitness, and which seem to demand an ethical response on both levels (i.e., the immediate and the long-term). Maybe epigenetics plays a role in genetic adaptation, and maybe it does not, but regardless epigenetics is changing our ethical environment at least as much as it shows our environment is changing us.
What do you think? How much does science also obligate us to act? At what point are we culpable for the knowledge we make? I am curious to hear your thoughts. Leave your comments below and I will respond.
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 Klengel, T. et al. 2013. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neurosci. 2013 Jan;16(1):33-41. doi: 10.1038/nn.3275. Epub 2012 Dec 2.
 References and links forthcoming