Epigenetics and the Importance of Being Random

Excerpt from my book Epigenetics and Public Policy The Tangled Web of Science and Politics now available from my publisher here and at Amazon

Although the physical conditions for mutation are well known,[1] so-called sporadic or spontaneous mutations[2] and other aberrations that occur during cell division are for the most part treated in conventional genetics as more or less random events. That said, there are significant debates as to what exactly is meant by “random” in this context. In more sophisticated discussions random is said only to indicate the nature of the statistical sampling of a population and not “indeterminism or any technical mathematical meaning.”[3] However, such technical explanations do not explain the links between the earlier invocation of random causes of variation made necessary by the assumptions of the insulation of organisms from their environment described at length in previous chapters, or the ongoing and now mostly tacit assumptions that mutations can be treated as random qua uncontrollable or unforeseeable events.

As discussed before, in general cancers are identified as the product of genetic mutations that are either passed on through the germline or acquired during one’s lifetime. Only a relatively few specific cancers are identified as the result of mutations from exposure to known carcinogens in the immediate environment, and none of these mutations are presumed to be heritable. In all other cases, these cancer-causing mutations are assumed to be functionally random events, both disconnected from their environments and not inherited. This dual recognition of some cancer-causing mutations as the product of environmental influences, but of all other mutations as somehow functionally insulated from the environment, is an awkward distinction that to my knowledge escapes not just scrutiny but general recognition within mainstream genetics and life sciences.

The origins of randomness

The primary scientific justification for this ultimate resort to randomness has its roots in the early days of the Modern Synthesis, and through population genetics in particular. Given the basis of population genetics in statistics, the assertion that mutations are inherently random seems to have originated primarily as a requirement of the mathematical formalisms being used to model how genes work (i.e., a rate of change needed to be specified in order for the equations being used to yield a result, and the assumption of randomness provided a convenient, mathematically simple, and empirically reasonable heuristic).

This approach was summarized in George Gaylord Simpson’s seminal Tempo and Mode in Evolution (1944),[4] which combined paleontology and population genetics through Sewall Wright’s theory of random genetic drift. This book was a pillar of the Modern Synthesis because of the way Simpson applied the statistical formulas from population genetics to examples from the fossil record and preliminary results from genetics. This assumption of the inherent randomness of mutations was then extended in the 1950s through the work of Motoo Kimura and his application to genetics of the Kolmogorov backward diffusion equation from physics, which models heat conduction as a random dynamic process and would go on to become a standard tool in population genetics.[5]

That the empirical results were fit to the mathematical formulas, and not the other way around, was a virtual necessity as there was not at the time any way to verify whether or not genetic mutations were in fact random qua causally disconnected from their environment—a theoretical difficulty which notably continues to this day.[6] In other words, the assumption of the actual randomness of mutations was not driven by any observations of the actual randomness of mutations (in fact, if anything, the available empirical evidence was that genetic mutations were actually produced by specific mutagens such as x-ray radiation[7]). Instead, this fundamental assumption was and is still driven by a priori theory and mathematical necessity, which are then used to inform subsequent theoretical and methodological choices in the development of the science of genetics.

Randomness and political ideology

As discussed elsewhere regarding Lamarckism and the emergence of modern genetics, this assumption of genetic mutations as random events—particularly as functionally disconnected from the environment—was one of the principal cudgels of neo-Darwinism against competing accounts of evolution and biological development. The conceptualization of mutations as random as “proven” by mathematics was a powerful way to justify describing the fundamental autonomy of humans from changes in their environments, in contrast to the neo-Lamarckism that was prevalent at this time which proposed that humans were quite malleable to their environments. As such, this notion of mutations as necessarily random (though, again, established as such more by a priori theory than through empirical observation) became a pillar of the Modern Synthesis of genetics, and still remains one of the central principles of contemporary genetics.

This is why, as also discussed elsewhere, one of Waddington’s primary motivations in initially proposing epigenetics more than 80 years ago was to expressly counteract this cornerstone assumption of genetic mutations as “totally unconnected with any ambient circumstances.”[8] Waddington saw this as such a fundamental concern in part because this scientific assumption of organisms and their environments as having “as little essential inter-relation as a sieve and a shovelful of pebbles thrown on to it,”[9] in turn carried with it substantial political implications, particularly regarding the relationships of humans with their environments and our responsibilities to each other.

Instead, for Waddington the work being done in embryology at the time clearly showed that organisms and their genes are essentially interconnected with their environments, and that an empirically valid science should reflect this relationship. As such, epigenetics was his attempt to reconcile and integrate the competing factions of genetics and embryology within a more comprehensive framework that incorporated the knowledge about the functioning of genes emerging from genetics with the knowledge about the role the environment played in the expression and function of genes. Although Waddington was manifestly unsuccessful in his attempt to realize a more holistic perspective for genetics, for all the reasons already discussed, the recent emergence of contemporary epigenetics—as demonstrated in this section in the domain of cancer—suggests that he was on the right track.

Some of the substantial political and ideological factors underpinning these choices to fit the theory of evolution and genetics to these specific mathematical formalisms, leading to this empirically unverified description of genes as practically insulated from their environments, have already been discussed. Still, it does bear noting again the degree to which these assumptions in the prevailing science of genetics mirrored similar political assumptions about the fundamental autonomy of human individuals in modern liberalism, and the role these philosophical assumptions played in the central ideological contest of this time between the liberalism of the West versus the collectivism of the Soviet Union. These geopolitical factors in turn also help to explain the specific direction the science took towards molecular genetics via this assumption of the inherent randomness of change in the genes in the absence of empirical observations—or, as in this case, actually against the only empirical proof available at the time.

Randomness, epigenetics, and the funding of science

Regardless, once this conception of mutations as inherently random gained traction and became the scientific consensus, it would go on to determine the subsequent definition of valid scientific work in genetics (i.e., work which reinforced and did not contradict this assumption of randomness qua insulation from the environment), and in this way determine the subsequent direction of research in genetics in the West, particularly as constrained by the structure of government funding for research described in chapters 8 and 10.

In particular, one concrete manifestation of this convergence of science and politics embodied in the assumption that the mutations of genes should be treated as random events is in the primary focus of cancer research over the past half-century. Instead of investigating the causes of mutations or other similarly “random” errors, the focus has been on identifying the control of genes over outcomes, or as the final or original cause in the causal chain resulting in cancer. Per Waddington this almost singular emphasis on genes as agents of control has pulled the designation of what is labeled appropriately “scientific” away from consideration of the greater contexts within which genes are nested. This scientific—and ideologically informed—conception of genes was only further reinforced by the distribution of the massive influx of government funding into science as funneled through increasingly narrow channels described in the previous chapter, which in turn influenced the subsequent direction of cancer science and research towards this specific conception of genes as controlling agents and away from consideration of the environments of the genes.

As such, the work being done in cancer epigenetics not only introduces substantial complications into the scientific understanding of cancer, and of genetics in general, in part by challenging the prevailing understanding of mutations as truly random, but in the process introduces even more substantial complications of the politics and policy of cancer because of the way it shifts attention back towards the nexus of genes and their environments. The effects of such a shift in attention could impact not only the distribution of funding, which would be a major political event within science in its own right, but also the greater policy responses to cancer which incorporate this new understanding of our connection to each other and to our environments.

[1] Lodish, H., Berk, A., Zipursky, S. L., et al. (2000). Mutations: Types and Causes. In Molecular Cell Biology 4th edition. New York: W. H. Freeman. Retrieved January 19, 2018 from https://www.ncbi.nlm.nih.gov/books/NBK21578/.

[2] Ibid.

[3] Millstein, Roberta L. (September 15, 2016). Genetic Drift. In The Stanford Encyclopedia of Philosophy (Fall 2016 Edition), ed. Edward N. Zalta. Retrieved April 20, 2017 from https://plato.stanford.edu/archives/fall2016/entries/genetic-drift/

[4] Simpson, G. G. (1944). Tempo and mode in evolution (No. 15). New York: Columbia University Press.

[5] Watterson, G. (1996). Motoo Kimura’s Use of Diffusion Theory in Population Genetics. Theoretical Population Biology. 49 (2): 154–188.

[6] Provine, William. (2001). The Origins of Theoretical Population Genetics: With New Afterword. 2nd ed. Chicago: University of Chicago Press; Millstein, R. L. (2008). Distinguishing drift and selection empirically: “The great snail debate” of the 1950s. Journal of the History of Biology, 41(2), 339–367.

[7] Gleason, Kevin M. (1926–1927). Hermann Joseph Muller’s study of X-rays as a mutagen. Embryo Project Encyclopedia (2017-03-07). ISSN: 1940-5030. Retrieved from http://embryo.asu.edu/handle/10776/11441

[8] Waddington, C. H. (1957). The strategy of the genes. London: Routledge, 188.

[9] Ibid.

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Epigenetics: From the Lab to the Law?

The extent to which the epigenetics research being done in cancer expands the causal circles of different cancers to include identifiable factors in the external environment is the same extent to which epigenetics not only exacerbates these ongoing political contests between advocates and scientists but also expands the politics to include all those parties with potential responsibility for these newly identified environmental factors. In addition, with the possibility of some epigenetic effects spanning multiple generations, this expansion of the political arena could include not only the issues and concerns of contemporary parties but also consideration of the circumstances of persons living decades if not centuries in both the past and the future.

These political disputes could conceivably introduce a wide range of issues that are not adequately addressed by our current legal and political principles—particularly those involving nonexistent persons in the conventional sense of personhood (e.g., either those long dead or not yet existing). For example, what is the appropriate level of protection of the privacy of the parents (or grandparents and great-grandparents) in the disclosure of their epigenetic information that might have substantial bearing on cancer diagnoses of their offspring, potentially many generations down the line? Particularly when this information may impinge on their own current circumstances?

Although these kinds of bioethical issues have already been raised in the context of genetic sequence data, the presumptively fixed and immutable nature of gene sequences shields the disclosure of genetic data from some of the thornier implications of epigenetics. For example, how are insurance companies to fairly allocate the risks of certain cancers with identifiable epigenetic causes that may only manifest generations later (i.e., who is justly responsible for the increased premiums necessary to cover the costs of such future health conditions)? Likewise, the possibility that epigenetic markers linked to the environmental contexts and personal circumstances of individuals of one generation may become a significant factor in assessing the responsibility for cancer in subsequent generations (e.g., as occupational exposure to specific pollutants, decisions to smoke, available dietary options related to culture and socioeconomic status) raises the stakes considerably in ways not anticipated by the current model of genetics and its corollary in the prevailing understanding of legal individuals as autonomous living beings.

Epigenetics in Court

Although epigenetics research has not yet been used as the basis of legal actions, consider the possible challenges to current conceptions of the family and the individual from the causal connections being identified via epigenetics. Suits have already been brought against parents on behalf of children suffering from fetal alcohol syndrome disorders (FASD)—for which the epigenetic pathways are already being identified[1]—because of the consumption of alcohol during gestation, which induced the FASD. One such suit was recently filed in Britain by an unnamed local authority on behalf of a seven-year-old girl in its care, claiming compensation on behalf of the girl from the Criminal Injuries Compensation Authority (CICA) for the reckless negligence of the mother, with more than 80 other claims on behalf of other children suffering from FASD awaiting the outcome of this case.[2] Notably, the local authority was awarded its claim in its initial hearing, but this decision was reversed by the Upper Tribunal of the Administrative Appeals Chamber on the grounds that “an unborn child is not a person in law and therefore no criminal offence could have been committed.” Again, as long as this is accepted as the standard and legal definition of personhood, then many of the inter- and trans-generational connections being revealed by epigenetics are moot as they deal with unborn persons which are technically not persons in law—despite their revealing of physical connections between the experiences and exposures of one generation with the physical conditions of subsequent persons.

However, one of the appeal court judges hearing the case described the law in this case as somewhat “incoherent” for its reliance on this conception of personhood as an exclusively postnatal identification when harms to an eventual person had obviously resulted from the negligent behavior of another person. Further, although the suit by the local authority on behalf of the child was dismissed on these grounds, this same judge also opined that “it’s not an entirely fanciful suggestion” that eventually the child as a legal person could still bring a private prosecution against the mother on her own behalf for the consequences of harms suffered while not a legal person.

At the same time, though, an officer of the CICA observed the dangerous precedent this more expansive legal interpretation of personhood would set, opening the door to suits in which “a pregnant mother who eats unpasteurised cheese or a soft boiled egg knowing there is a risk that it could give rise to a risk of harm to the foetus” could be subsequently accused of a crime by the resulting child. From allowing such claims of harms inflicted in utero, it is only a small conceptual leap toward allowing claims of harms inflicted ex vivo (for lack of a better phrase). To the degree that such connections between present actions and future consequences can be established scientifically via epigenetics, a tidal wave of legal claims would potentially arise of children against parents, grandchildren against grandparents, and so on, introducing unprecedented and far-reaching legal and political complications into the mix.

Epigenetics and ‘Wrongful Life’ Claims

Granted, this example of FASD is not an example of epigenetics in cancer but the extent to which similar causal pathways for cancer could be identified via epigenetics is also the extent to which similar legal and political complications would arise, only for each form of cancer for which these causes are identified. One currently accepted legal action that might apply to such claims relying upon these epigenetic pathways for cancer is the legal doctrine of “wrongful life,” from the landmark California Court of Appeals decision in Curlender v. Bio-Science Laboratories (1980)[3] that involved the issue of the reliability of genetic screening for congenital disorders. The most famous and relevant passage of the Curlender opinion states:

The circumstance that the birth and injury have come hand in hand has caused other courts to deal with the problem by barring recovery. The reality of the “wrongful-life” concept is that such a plaintiff both exists and suffers, due to the negligence of others. It is neither necessary nor just to retreat into meditation on the mysteries of life. We need not be concerned with the fact that had defendants not been negligent, the plaintiff might not have come into existence at all. The certainty of genetic impairment is no longer a mystery. In addition, a reverent appreciation of life compels recognition that plaintiff, however impaired she may be, has come into existence as a living person with certain rights.

That the California Court of Appeals reasoned—contrary to the Administrative Appeals Chamber in Britain—that fetuses exposed to certain harms become living persons manifesting the effects of those harms demonstrates both the subjectivity of these kinds of metaphysical distinctions but also the legal implications of rulings in one direction or the other. However, given these differences in interpretations of philosophical concepts such as “life” and “personhood,” wrongful life claims are currently only allowed in a few states in the United States, and are also not widely recognized internationally. That said, to the extent that epigenetic pathways for cancer can be identified, the precedent of Curlender at least opens the door for the assertion of “epigenetic impairment” due to the negligence of others—even those separated in both time and space—as a legally recognizable condition.

Epigenetics and the Discovery of Harm rule

The legal implications of hypotheticals like this may not be as far-fetched or as far away as it might seem. Consider the potential application of the Discovery of Harm Rule which is an already an accepted legal precedent, which holds that while a statute of limitations may set temporal restrictions on the filing of personal injury lawsuits after an accident or injury, these time periods do not begin to run until the persons filing suit become aware that they had suffered harm, or that the nature of that harm was realized. This rule suggests that to the extent that the research in epigenetics is able to establish these kinds of causal connections to a reasonable certainty, or even to a probability, there is likely to be an avalanche of legal actions brought forth on these grounds.

The combination of the increasing legal acceptance of wrongful life claims—which involves a reconception of the nature individual suggested elsewhere—with the application of the Discovery of Harm rules in the context of the multi-generational transmission of effects established via scientific work in epigenetics could potentially swamp our legal, political, and financial systems. All this is not to mention the legal and political complications that could arise if the initial exposures occurred within one political jurisdiction (i.e., a state or a country), perhaps generations prior, but the effects are only now being realized in a different political jurisdiction. And so on.

The sheer, dizzying magnitude of these potential consequences suggests the external pressures that could be brought to bear on the development of the science of epigenetics over the next few years, as any number of corporations and government entities would have vested interests in discouraging the discovery and the reporting of such connections. An actual example of this dynamic in action is the acrimonious and litigious reaction from the pesticide industry to the work from the Skinner Laboratory, in the Center for Reproductive Biology at Washington State University, on the epigenetic heritability of the effects from vinclozolin, a widely-used fungicide.[4] Notably, these kinds of results were not initially disputed when the focus of the Skinner Lab was on the pesticide methoxychlor, a known endocrine disruptor, which has been banned from use for years.[5]

To assume that the science would advance unencumbered by these political concerns—especially given the history detailed in previous chapters—would be inexcusably naive. Still, the highly political aspects of epigenetics are thus readily apparent, as is the magnitude of the potential repercussions.

Granted, the actual result of the research in epigenetics could be that eventually the possibilities indicated by this initial work—such as the linking of factors in the environment more directly with gene function, and the potential for transgenerational inheritance of epigenetic effects—do not pan out as initially expected. In this case the political repercussions would be much more muted than suggested in this book. However, given the development of the science of epigenetics thus far, outcomes like the scenarios just described are not only conceivable but increasingly plausible.

[1] Chater-Diehl, E. J., Laufer, B. I., Castellani, C. A., Alberry, B. L., and Singh, S. M. (2016). Alteration of gene expression, DNA methylation, and histone methylation in free radical scavenging networks in adult mouse hippocampus following fetal alcohol exposure. PloS One, 11(5), e0154836.

[2] Bowcott, O. (November 5, 2014). Foetal damage caused by alcohol “equivalent to attempted manslaughter.” The Guardian. [online] Retrieved July 28, 2017, from https://www.theguardian.com/law/2014/nov/05/foetal-damage-mother-alcohol-manslaughter

[3] Curlender v. Bio-Science Laboratories, 106 Cal. App. 3d 811 (1980).

[4] Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013100); Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933025/); Shifting the Genetic Paradigm with Epigenetics (https://www.aaas.org/blog/member-spotlight/shifting-genetic-paradigm-epigenetics)

[5] http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102091

Why Epigenetics and Politics? The Response

To begin my response to this excellent comment on a previous post, I think I need to point out a couple of different aspects of my approach to epigenetics (which I explain in much more detail in my book) that are germane to the questions asked and observations made in this critique.

In general, there are two main emphases for my interests in epigenetics: the scientific side, and the political/philosophical aspects. These are necessarily related to each other in many different ways (e.g., the political and philosophical aspects would not exist without the scientific work being done in epigenetics, just as politics has had a substantial influence on the development of the science—again, a major focus of my book), but they can also be quite disconnected from each other in different contexts (e.g., political uses can be made of the science which ignore important findings or critical assumptions).

Given how intertwined the science and the politics can be, though, it is often difficult to separate them and their effects or influences in different domains, but this is the crux of much of my approach. In this sense, on the one hand, some of my arguments are contingent on the eventual validation of controversial scientific issues, such as true transgenerational epigenetic inheritance. On the other hand, just the revelation of enhanced interconnectivity with each other and with our environments via epigenetics introduces substantial political complications, not to mention just the possible political uses to which even invalid interpretations of epigenetics could be put.

Epigenetics and policy

Regarding the observations about the low likelihood of policies to restrict individual choice based on scientific or medical research as evidence against the notion that epigenetics might have a substantial effect on public policies, in a pure bolt of serendipity, just after I read this comment someone posted an extensive thread on my Twitter feed loaded with references on just this issue of ‘crack babies,’ and particularly about the differences in framing and policy narratives due to politically salient issues such as race (here: http://bit.ly/2KQHWFh). I also did a quick Google search on “criminalization of drug use during pregnancy” (http://bit.ly/2wrpvE4), which came up with 31,900,000 results about all the different ways that this kind of thing is actually a substantial focus of public policy and government action.

While on the one hand it might be that—for now—there are not any formal criminal laws about mothers for their actions during pregnancy, there are still multiple ways in which this is very much a concern of the State, and in which scientific research and medical evidence directly informs policy. For example, from the American College of Obstetricians and Gynecologists in 2011 (and reaffirmed in 2014):

Although no state specifically criminalizes drug abuse during pregnancy, prosecutors have relied on a host of established criminal laws to punish a woman for prenatal substance abuse. As of September 1, 2010, fifteen states consider substance abuse during pregnancy to be child abuse under civil child-welfare statutes, and three consider it grounds for involuntary commitment to a mental health or substance abuse treatment facility.[1]

Likewise, another more recent article describes how prenatal drug use is now considered child abuse in 23 states, and how in 2014, Tennessee passed a “fetal assault” law that criminalized drug use during pregnancy based on the ruling of a district court judge that such actions constituted “substantial risk of harm to a minor,” which decision was subsequently endorsed by a federal level U.S. Attorney as valid precedent for sentencing guidelines.[2] There are also laws in most states dictating that physicians can or even must release the drug test results of expectant mothers to law enforcement without the authorization of the mothers, and so on.

And all this is just in the domain of drug use during pregnancy—for example, more broadly, there are an increasing number of legal actions being brought by children against their parents based on ‘wrongful life’ claims which I detail more extensively in my book, and which I excerpt here. As such, I think this comment greatly underestimates the number of different ways that policy happens and thus the potential for the timbre of these laws and policies to change in reaction to emerging scientific evidence like epigenetics—especially when that evidence can be used to affirm preexisting biases or realize politically expedient outcomes.

These kinds of policies are already being made and promoted under the more conventional understanding of genetics, in which biological cores are assumed to be more or less fixed, such that things like prenatal drug use constitute ‘accidents’ on this fixed biological substrate.[3] My primary interest in these areas pertaining to epigenetics is how much these public and State responses might change in response to valid—or even invalid—information that this biological substrate is not as inviolate as has been assumed? The history of the development of the science of genetics with the virtual exclusion of epigenetics until quite recently, which is a main focus of my book, repeatedly demonstrates changes in politics and policy coincident with changes in the science, and vice versa. As such, these kinds of contemporary questions are just extensions of this history.

In addition, given the current state of affairs, I am curious about the urgency and the manner with which such issues might be addressed in the light of something like true transgenerational epigenetic inheritance. If these kinds of policies are being promoted now, when the only ‘victim’ being implicated is the one fetus, what kinds of policies could result from the exponential expansion of this circle of ‘victims’ to include multiple generations? If there are significant costs to be borne in the future from this exponential expansion of the scope of impact, there will inevitably be political conflicts over who should be morally and fiscally responsible for those consequences. And so on. There are obviously no solid answers to these questions yet, given the state of both the science and contemporary public policy, but my project is to begin to ask these questions now in the case that the science of epigenetics begins to make its way into the public policy domain.

Epigenetics and philosophy

I also assert that there is a coherent underlying rationale for these kinds of political actions, from the legal doctrines or principles that are deployed in courts to the largely unspoken implicit assumptions of people in society at large. This turns the focus to the more fundamental philosophical issues at hand, because of the ways these political decisions reflect specific underlying assumptions about the nature of the individual, and of the relation of individuals with their environments and with each other.

In the context of the underlying philosophical underpinnings of America in particular, I will agree that the Founding Fathers did not mean equality in a genetic sense, primarily because how they conceived of biology or the inheritance of traits does not translate readily into our contemporary concepts. However, I will disagree that they meant a primarily spiritual equality, or that they intended equality as the erasure of “biological or factual inequalities” such that all persons (or even just men) should considered literally equal, though explaining this line of thought is a complicated circuit to complete.

There is a much more extensive discussion to have on this point,[4] but for now I will say that my reading of Enlightenment thought, and particularly of the nascent conception of human biology of the prevailing figures of this era including the Founding Fathers, was that the human body was much more open to the environment than we now think, but also that there was a natural hierarchy. For most of them, per the thought of John Locke, etc., the goal of refashioning government was to reconfigure the environment so that the natural tendencies of people were allowed to flourish. That said, they also thought of themselves and those of their ilk as natural aristocrats who were being stymied in their development by a monarchy, so removing those strictures would allow their class to naturally rise. At the same time, they very clearly perceived and described the common folk as naturally much less capable for tasks like government, which should be left to the natural aristocrats, though republican government would allow even these common people to more fully realize their much more limited capacities than under a monarchy.

Although this is a much different conception of biology and politics than our own, our current conceptions of ethics, politics, and of biology—which are all based on a much more atomistic conception of the individual—did develop out of this way of thinking, so there is a ‘genetic’ inheritance of sort from their thought to ours. The process through which their prevailing conceptions evolved into our currently predominant conceptions of science and politics is a major focus of my book, constituting the entire middle section. The end result, though, is the distinct emphasis on the unique conception of the individual that is characteristic of modern liberalism writ large, and the basic assumptions of the sciences which developed apace with modern liberalism and this conception of the individual.

As I go into much more detail elsewhere, to us modern liberals in the West this conception of the individual feels self-evidently true, so much so that its underlying assumptions are now practically invisible to us. However, all of this is very much a contingent product of a specific intellectual and cultural history. Other cultures, for example, developed with much different conceptions of the individual—and therefore of society—resulting in much different ethical, political and even scientific traditions. These fundamental philosophical differences were the focus of my research as a postdoctoral fellow at the Center for Comparative and East Asian Philosophy in Hong Kong—in particular regarding the unanticipated congruencies between East Asian conceptions of the individual and the scientific knowledge coming out of epigenetics.

For example

One area which aptly illustrates these political and philosophical complications from epigenetics is in the reprogramming of the parental genomes after fertilization. It is well-established that the genes of embryos undergo waves of ‘washing’ to ostensibly remove the epigenetic markers of the parents, or the residue of their environmental exposures and other experiences, thereby rendering a now pristine genome (i.e., one returned to its original condition).[5] To assert the congruence of this conception of a washed genome with the Lockean conception of people being born as Blank Slates, to then be constructed through their own experiences and not as the product of the experiences of their predecessors, does not seem as much of a stretch suggested in this comment, especially given the common history of these ideas. That this Lockean conception of people as fundamentally free and independent individuals is a cornerstone of modern liberalism also seems an uncontroversial assumption.

As such, any complication of the understanding of the biology on this point is equally a complication of one of the basic premises of modern liberalism. Work being done in epigenetics is suggesting and now even showing that not all of these epigenetic markers are always being scrubbed or reset during these stages, and that other epigenetic errors are accumulating and propagating during these processes, resulting in significant gene-level defects in development, but not from alterations of DNA sequences.[6] Work is also being done to link these types of early epi-genetic anomalies to health outcomes later in life, along the lines of the Developmental Origins of Health and Disease (DOHaD) hypothesis.

Thus, to the question about how these epigenetic causes would be different from other environmental and genetic factors resulting in less than optimal outcomes, my main point in this regard in a politics and policy context pertains to the connection to the environment that is being explored or exposed by the work in epigenetics. In particular, I am interested in the potential for determining and assigning responsibility for health-related outcomes via epigenetics. We already have ways of describing and discussing inheritance of behaviors from environmental exposures (e.g., psychology), which also involves determining responsibility, and which are also usually based on this prevailing concept of the unitary individual. Likewise for genetics, although what is particularly interesting in this regard is that conventional genetics usually obviates the assignation of responsibility for such outcomes as being either indelibly fixed or random (i.e., beyond human control).

What I suggest is that we don’t yet have similar explanations in place for epigenetic-type phenomena, which are different enough from the conventional psychological and genetic explanations to require their own responses. As such, the degree to which causal connections can be established via epigenetics between the actions of persons or entities at one point in time with the health-related experiences of individuals of a subsequent time would present substantial complications for conventional politics and policymaking, at least until such responses are eventually institutionalized. My project, then, is to begin the discussion of what these political responses might or should be.

Once again, I want to thank the person who left this extensive comment on my work, which provided me this opportunity to (hopefully) explain and justify why I think the political implications of epigenetics are a worthy topic for discussion, even at this early moment in the emergence of the science involved in epigenetics. I hope I was able to answer at least some of her questions.

[1] Substance abuse reporting and pregnancy: the role of the obstetrician–gynecologist. Committee Opinion No. 473. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;117:200–1.

[2] https://www.drugaddictionnow.com/2017/01/20/legal-consequences-using-drugs-pregnant/; This law was also subsequently repealed, but that it was passed at all, and that the original court decision was endorsed by a federal level official indicates that such outcomes are possible, and also seem to be indicative of a growing trend.

[3] There is a very extensive discussion implied here regarding these ‘accidents’ on fixed forms that basically involves the central thrust of Western cultural and intellectual history from the Greeks through today, and particularly through Aristotle and Aquinas, that I have written about elsewhere, but which I cannot delve into at this point.

[4] I go into much more detail about this point in my recent conference paper “Radical Bodies: The Political Biology of the Enlightenment and Contemporary Political Theory” that I presented at the recent Midwest Political Science Association annual conference. The basic gist, though, is that there were at least two major streams of Enlightenment thought, the Mainstream or Moderate version, and the Radical Enlightenment. From my reading, Western intellectual and cultural history developed from out of the Moderate Enlightenment, but employed Radical rhetoric (the intellectual justifications of the American ‘Revolution’ being a prime example of this). The central point of this paper is that the primary differences between the two Enlightenments revolve around their differing conceptions of the human body. For the Moderate Enlightenment, the human body and mind (or spirit or soul) were increasingly conceived as atomistic and autonomous. From out of this conception of individual unity and autonomy, I assert elsewhere, have developed contemporary psychology, politics, and science of genetics. In contrast, the thinkers of the Radical Enlightenment promoted a much more porous and interconnected conception of the individual, which I assert is much more congruent with recent developments across a number of sciences, including epigenetics in genetics.

[5] To wit, the point that some of these embryonic genes might be altered in some way, resulting in Down’s, Williams’, or Klinefelter’s Syndromes, seems a non sequitur in this context, as ‘pristine’ of itself does not require perfection or purity (these are synonyms, but something can be pristine qua restored to its original form and not perfect or pure). Otherwise, I would have to be asserting that equality in this sense means that everyone is born perfectly ‘normal’ at the genetic level, instead of that their genomes are presumed to be rendered as blank slates.

[6] For example, see http://genesdev.cshlp.org/content/28/8/812.full for a recent review

Why Epigenetics and Politics? A Critique

This post is the reposting of a comment from EvolutionistX to a previous blog post of mine (Epigenetics and Ethics: Rights and Consequences). Given the length of her comment, I thought the best way to present it would be as its own post. She has also posted a more extensive reply on her own blog, located here

I am posting this comment because I think in her criticisms she gets to the heart of what I am trying to say about the political implications of epigenetics. I will also post my reply as a follow-up to this comment. I also want to thank her again for taking the time to read and engage with what I’ve written enough to write such a detailed commentary, and for asking such probing questions. I appreciate when my work is taken this seriously even, as in this case, when that attention is more critical.

Hello, and thank you for pointing me to your blog. I haven’t read it all, so forgive me for jumping in prematurely.

I’m not sure epigenetics constitutes such a fundamental shift in our understandings of genetics and inheritance as to actually warrant much change in our present policies. For example, you question whether policies should be enacted to restrict a 12 yr old girl’s right to eat what she wishes in defense of her unborn grandchild’s epigenome, but we today don’t even restrict a pregnant woman’s right to drink or smoke. Cocaine is illegal, but last time I checked, women didn’t go to prison for giving birth to crack babies. For that matter, women are allowed to kill unborn babies. I’m not commenting pro or against abortion, just noting that it is legal and most people consider death kind of a big deal. So I don’t think society is about to start outlawing stuff because of its negative effects two generations down the road.

On the other hand, if you look at the data on smoking, rates have definitely been falling ever since the tobacco-cancer link became news. The gov’t didn’t have to outlaw smoking for a lot of women to stop smoking for their children’s health.

But let’s return to the philosophical argument. All men are created equal… or are they? I do not think the Founding Fathers ever meant equality in a genetic sense. They could see with their own eyes that some men were tall and others short, some wise and others foolish, some virtuous and others criminal. They could see see that sons and daughters took after their parents and that a great many people started life in horribly unfair circumstances while others lived in luxury. They could see the cruel unfairness of disease, disability, and early death. Their rejection was not of biological or factual inequalities but of spiritual inequality. They rejected the notion that some men are created special by God to rule over others, and some men are created inferior by God, to be ruled over.

You state, “However, the evidence emerging from epigenetics suggests this is not the case. Instead of individuals of each generation being born with a pristine copy of their biological essence, they are inheriting a genetic endowment riddled with markers of the experiences of their parents and grandparents and great-grandparents, and so on. And these inherited epigenetic markers, as more and more research is showing, are having direct effects on the physical and mental health of individuals from causes not actually experienced by these individuals.”

I think there is a mistake here in regarding genetics as “pristine” in some form. What if my mother is an anxious person, and I, through environmental exposure, grow into a similarly anxious person? What if my mother has a gene for anxiety, and I inherit it? What if I possess a de novo genetic mutation that causes me to be anxious? And what if I suffer a genetic deletion in one of my chromosomes that causes anxiety? How is any of this different, functionally, from some trauma my mother suffered (say, a car accident) causing epigenetic changes that are subsequently passed on to me?

What is pristine about Down’s Syndrome, Williams’, or Klinefelter’s? Or just having the random bad luck to get genes for short, dumb, and ugly?

“For example, research in epigenetics shows that the choices and experiences of individuals in one generation are conditioning the basic nature of individuals of subsequent generations, which indelibly affects how those new individuals will exercise their own rights. ”

It can’t be indelible. For starters, you only inherit half of each parent’s genome–thus half their epigenome. So right there’s a 50% chance you won’t inherit any particular epigenetic marker. By gen two we’re talking 25% chance, and that’s not counting the constant re-writing of our epigenomes. However, I don’t think the policy implications for countries are all that different from our current thinking. We can say, for example, “If we have X level of pollution in the water, then Y number of people will get cancer,” and it’s a public health problem even if we don’t know “they’ll get cancer because of epigenetics.”
So let’s broaden the inquiry a bit. Not how does epigenetics impact classical liberalism (which is behind us, anyway,) but how do genetics, epigenetics, heritability, et at all influence our modern sensibilities? Modern liberalism is built almost as a reaction against former racialist notions of “blood”, with a consequent belief that people are, on average, about genetically equal. This butts up against the realization that some people are gifted and talented from birth, which many people quietly rationalize away while knowing they are being a bit dishonest, perhaps on the grounds that this is tantamount to statistical noise.

But the whole notion of “meritocracy” becomes more problematic if we admit that there’s a large genetic (or accidental, or environmental, or anything outside of free will,) contribution to IQ, educational attainment, mental illness, your chances of getting a good job, how other people treat you (because of attractiveness,) etc. Should a person who is dumb through no fault of their own suffer poverty? Should an ugly person be denied a job or a date? There’s an essential unfairness to it, after all.

But by the same token, what are you going to do about it? Declare that everyone under a certain IQ gets free money? What sort of incentives does that set up for society? And what does it do to someone’s self-image if they are Officially Delcared Stupid?

But this is all focused on the negative. What if we find ways to make people smarter, healthier, stronger? I think we’d take them. Sure, we’d have a few hold-outs who worry about “playing god,” (much as today we have people who worry about vaccines despite the massive health improvements public vaccination campaigns have cause.) But in the end we’d take them. Similarly, in the end, I think most people would try to avoid damaging their descendants’ epigenomes–even if not through direct public policy.