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Social Epigenetics and Equality of Opportunity

Social Epigenetics and Equality of Opportunity Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 PUBLIC HEALTH ETHICS VOLUME 6 NUMBER 2 2013 142–153 142 Social Epigenetics and Equality of Opportunity Michele Loi , Center for Translational Genomics and Bioinformatics, CEHUM, Universidade Do Minho and San Raffaele Scientific Institute Lorenzo Del Savio, Istituto Europeo di Oncologia Elia Stupka, Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute Corresponding author: Michele Loi, Centro de Estudos Humanı´sticos, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Tel.: (+39) 320 027 3272; Email: loi.michele@ilch.uminho.pt Recent epidemiological reports of associations between socioeconomic status and epigenetic markers that predict vulnerability to diseases are bringing to light substantial biological effects of social inequalities. Here, we start the discussion of the moral consequences of these findings. We firstly highlight their explanatory importance in the context of the research program on the Developmental Origins of Health and Disease (DOHaD) and the social determinants of health. In the second section, we review some theories of the moral status of health inequalities. Rather than a complete outline of the debate, we single out those theories that rest on the principle of equality of opportunity and analyze the consequences of DOHaD and epigenetics for these particular conceptions of justice. We argue that DOHaD and epigenetics reshape the conceptual distinction between natural and acquired traits on which these theories rely and might provide important policy tools to tackle unjust distributions of health. As we explain at length below, epigenetics is defined Introduction as the study of the inheritance (between cells and/or In this article, we assess the implications for justice and organisms) of traits (gene expression or phenotypes) health of the developmental origins of health and without changes to the underlying DNA sequence. As disease (DOHaD) hypothesis and findings in epigenetics we shall indicate, there are three features of epigenetic that corroborate it. Other articles have addressed traits that make them important for a normative analysis the ethical and social consequences of epigenetics of health inequalities: (Rothstein et al., 2009; Drake and Liu, 2010; Hedlund, 2012), arguing that the fight against epigenetically  Sensitivity to social structures: Some epigenetic transmitted forms of disadvantage is more a political phenomena are highly responsive to environmental than an individual responsibility. In this essay, we changes, which are affected by social institutions. discuss the scientific evidence on which this claim is  Early programing: Several epigenetic traits are based and defend a case for public health interventions established early-on in development, and their effects based on epigenetic discoveries in a framework of on health unfold throughout the life course. equality of opportunity. Because the concept of equality  Trans-generational transmission: There is evidence of opportunity is interpreted in different ways by differ- in both animal models and epidemiological ent moral traditions, we analyze the luck-egalitarian and studies that epigenetic traits can be trans- the Rawlsian versions showing that the two overlaps generationally inherited. In addition to genetic significantly in this context. inheritance that provides adaptive flexibility in Recent discoveries in epigenetics improve our under- the long (evolutionary) time span, epigenetics standing of how individual health and therefore oppor- constitutes other, semi-stable, biological mechan- tunity is affected by early developmental events and isms through which features are inherited previous generations’ environmental circumstances. through generations. doi:10.1093/phe/pht019 ! The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 143 In virtue of the three features above, epigenetics mechanistic base of developmental programing? provides a chain of connections between what used to Epigenetics, the study of mitotically (or meiotically) be qualified as social and natural inequality, leading to a heritable changes that alter gene expression and pheno- reformulation of these contested boundaries. This also types, but are independent from the underlying DNA leads to a rethinking of the time-frame and scope of sequence, can provide some answer to this important equality of opportunity. question (Gluckman et al., 2008). Epigenetics is the study of semi-stable molecular states (e.g. life long and transmissible over a limited number of generations) that Epigenetics and Health influence physiology in subtle ways during develop- Inequalities ment, in physiological conditions and in the establish- ment of several diseases. Also, they are sensitive We begin this review of the public health implications of to environmental clues rather than being exclusively epigenetics by situating a discussion of epigenetic mech- endogenously determined and provide biological anisms into the broader context of the social determin- systems with flexibility, the capability to respond to ants of health inequalities. environmental challenge and rudimentary ‘learning’ The incidence of several diseases is negatively corre- mechanisms. Both stability and sensitivity to the envir- lated with socioeconomic status (SES), as measured by onment are features that render epigenetics an eligible income, wealth and educational level and independently mechanistic explanation of early programing. from the universal public provision of health services. Indeed it is this semi-stability or relative stability to This striking epidemiological phenomenon is illustrated confer such a pivotal role to epigenetics in a revised by the city of Glasgow, UK, where people in the poorest understanding of natural traits and response to envir- neighborhoods expect to live 12 years less than their onment. Indeed, epigenetic biological phenomena are counterparts in the richest parts of the city. Poverty ex- slower than continuous dynamic gene expression plains only part of these disparities: a steady gradient of changes affecting cells and organisms in their daily health outcomes across social classes has been observed lives, yet faster than genetic inheritance and fitness, for many conditions, even among groups that are fully which occur at a slow pace over a large number of gen- above the threshold of poverty (Marmot, 2005). erations. At the same time they are able to respond to Neither the steepness of the health gradient nor the sustained environmental stimuli, and can be inherited magnitude of these disparities can be accounted for by through several, but possibly not many, generations. the social stratification of a single kind of risk factor. These characteristics taken together place epigenetics Rather, material (e.g. poverty), behavioral (e.g. diet), in a unique position in reshaping our understanding biological (e.g. blood pressure) and psychosocial (e.g. of how natural traits, traditionally viewed as heritable stress) pathways may add up and interact to establish traits selected through countless generations during social health inequalities (Arendt and Lauridsen, 2007; evolution, might actually evolve in a more dynamic Blane, 2006). manner as a response to environment, and thus, in the In our review we focus on the early life effects of SES. case of humans, to social environments. In ‘DOHaD and epigenetics’ section, we introduce the The paradigmatic epigenetic phenomenon, in concept of ‘DOHaD’, the role of epigenetics as a mech- fact one that has been discovered early on, is DNA- anism for DOHaD, and for the inheritance of acquired methylation, the addition of a methyl group to a DNA predispositions (in a quasi-Lamarkian fashion). In cytosine residue, initially thought to occur mostly at ‘Case-studies’ section, we discuss two specific cases in cytosine-guanosine dinucleotides (CpGs) in promoter more detail: nutrition and parenting style, associated, regions of genes, but now understood to be a more respectively, with metabolic diseases and psychological widespread phenomenon occurring throughout the conditions. In section ‘Social epigenetics’, we provide genome also at non-CpG nucleotides (in embryonic some evidence of the social stratification of epigenetic stem cells) and away from promoters (in intergenic differences between individuals. regions). Changes in the DNA-methylation patterns at the genomic level are involved in the regulatory control DOHaD and epigenetics of gene expression in mammalian development and in The concept of ‘DOHAD’ has been introduced to the development of several human physiological traits describe exogenous influences on early development as well as diseases. This epigenetic modification has its that may predispose the organism toward specific own control machinery, a set of enzymes (DNA methyl phenotypes or diseases (Barker, 1995). Which is the transferases), which generate de novo methylation Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 144 LOI ET AL. patterns, as well as controlling the maintenance of adaptive if food scarcity is endemic, but becomes ‘mal- DNA-methylation patterns throughout development. adaptive’ when it matches poorly an environment where Although in mammals DNA-methylation is repro- there is plenty of high-energy foods. Similarly, a high-fat gramed in the earliest phases of development (first maternal diet programs her offspring for increased risk days after conception around the time of in utero of adult obesity or metabolic disorders in childhood implantation of the embryo), there is evidence of (Chmurzynska, 2010). Both these mechanisms may be trans-generational persistence of DNA-methylation relevant for the early-programing hypothesis in life- signatures (i.e. imprinting), which are also involved in course social epidemiology, in fact in two different the development of certain developmental conditions. contexts of sharp disparities in health outcomes. The Recent advances in sequencing techniques (i.e. association between early undernourishment and meta- next-generation sequencing) rendered possible the bolic disorders may explain the sharp increase in the high-throughput screening of genome-wide DNA- prevalence of the latter in emerging economies, which methylation patterns, thus providing the first genome- in fact experience a ‘double-burden’ of diet-related con- wide maps that will allow us to correlate molecular ditions (Popki, 2001). The association between maternal differences at the epigenetic level and significant health hypernutrition and children conditions is instead im- parameters, such as the susceptibility to cardiovascular portant in high-income countries, where obesity is so- diseases (CVDs). Thanks to next-generation sequencing, cially stratified and especially so among women: aside we are now also able to explore in a more complete from behavioral channels of transmission of childhood manner other types of epigenetic signatures beyond obesity, which is predicted by parental body max index, DNA-methylation, i.e. those based on histone modifica- programing may be partially responsible of this ‘inher- tions (histone methylation, acetylation, etc). The itance’ of the condition (Sullivan et al., 2011). number of modifiable histones, and the number of Epidemiological studies have also begun indicating modifications observed so far have brought the scientific intergenerational transmission of DOHAD effects (i.e. community to point to a ‘histone code’ because of observing a grandfather to grandson DOHAD effect) its potential complexity. Nonetheless histone modifica- (Kaati et al., 2007). These have been investigated in tions have already been shown to be involved in greater depth and across more generations in animal epigenetic inheritance and epigenetic control of gene models. A study of a low-protein diet in rats, for ex- expression. ample, has indicated that the phenotypic effects of the In conclusion, epigenetic mechanisms appear to be diet given to the so-called F0 generation (i.e. the first set involved in the early programing of adult phenotypes of parents from which the experiment starts) are indeed and the transmission of molecular phenotypes across observed not only in the F1 (i.e. in their children), but generations. In the next section, we will discuss the also in the F2 (i.e. their grandchildren) and finally the empirical evidence bearing on two classes of cases: meta- phenotype is lost in the F3, underlining the semi-stable bolic disorders and psychological conditions. heritable behavior of this programing effect (Harrison and Evans, 2009). Moreover, it was shown that the effects on hypertension of low-protein diet during fetal life were Case-Studies reversed on administration of pharmacological com- Maternal diet and adult outset diseases pounds blocking maternal glucocorticoid synthesis predispositions (Langley-Evans, 1997). Both the human cohorts and A paradigmatic case of the relevance of epigenetic animal models have been investigated in terms of the programing for adulthood diseases is nutrition during potential epigenetic mechanisms involved in the pregnancy (Sullivan et al., 2011). Subtler features of diets DOHAD effect providing early clues to the role of may program the newborn for conditions that will be DNA-methylation (reviewed in Mathers et al., 2010). visible only in adulthood. Both undernourishment and Parenting style and psychological conditions hypernutrition have been proposed to be influences of this kind. As for the former, in the studies of the popu- Health is important in its own right as for life opportu- lation affected by the 1944–45 Dutch famine maternal nities. Also, poor health is associated with lower educa- undernourishment was shown to be a predictor of tional attainments and therefore health is partly susceptibility to type II diabetes. Based on this, Neel responsible for the association between being born in (1962) proposed that maternal malnutrition may act as a poorer family and lower educational achievements an environmental switch that turns the metabolic system (Case et al., 2005). The latter are a crucial predictor of of the developing fetus in a thrifty mode, which is employment status and income, and therefore health Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 145 does impinge on opportunities in at least two ways: mechanisms, environmental insults in early infancy may directly and through educational careers. program future metabolic and psychological pheno- Moreover, there is a broader class of conditions that types later in life (DOHaD); moreover, environmental are certainly relevant for life opportunities and for insults experienced by parents and grandfathers can which epigenetic mechanisms might be responsible as be transmitted to children and grandchildren (inter- well: psychological conditions. In particular, stress generational inheritance). responsivity, cognitive ability and response to reward Evidence of direct inheritance is still sparse and open are highly sensible to early-life events, especially mater- to empirical scrutiny (Daxinger and Whitelaw, 2010). nal care (Champagne, 2008). Because these are also On the other hand, early programing could represent an features that will influence opportunities, recent discov- indirect way in which health disadvantages are acquired eries on the biology of early life circumstances and and passed on from parents to children. This inter-gen- psychological conditions might open up new policy erational stability of certain conditions is already known avenues to tackle disadvantages. in social epidemiology at the statistical level. Behavioral This DOHAD effect has also been furthered by and socio-structural channels of inheritance may ac- experiments with animal models. A study on rats’ count for this stability: children from poor backgrounds mothering styles gave some hints about how this might encounter social environments that are similar to their work (Weaver et al., 2004): the stress response mechan- parents’ and learning is a major pathway of inheritance ism is tuned by maternal behavior in early life and it also of unhealthy lifestyles. Jablonka and Lamb (2005) expli- leads to permanent changes in DNA-methylation and citly juxtaposed epigenetics and ‘cultural’ inheritance, histone acetylation of genes that are involved in stress fleshing out an analogy based on their inter- and response. The main idea beyond the discovery is that intra-generational stability and their sensitivity to maternal parenting style changes profoundly the physi- exogenous clues. Their ideas include the hypothesis ology of the rat pups, triggering a cascade of molecular that there could be more channels over and above cul- events that get written on their epigenetic code thus tural inheritance (e.g. learning) and genetics that explain modulating gene expression in adulthood. The re- how traits are inherited from parents to their offspring: searchers studied a phenotype of mothering behavior, in particular, epigenetics mechanisms would be sensitive frequent licking and grooming (high-LG), that was asso- to environmental clues, similarly to what happens in the ciated with high level of hippocampal glucocorticoid case of learning, while being at the same time relatively receptor activity, which is related to stress response. stable through time, as in the case of genetics. Their Because upregulated stress response is in turn asso- hypothesis replaces the distinction between innate bio- ciated with high-LG mothering style in adulthood, the logical traits and flexible learned traits with a continuum study provided the description of an epigenetic trans- of biological traits that are more or less programable by generational inheritance of a behavioral trait (Sapolsky, environmental clues and reprogramable by post hoc 2004). For our purposes (see section ‘Reversible and interventions. Epigenetics is thus a sui generis channel preventable epigenetic predispositions: correcting early of inheritance, which shares features both with genetics disadvantage as investment’) it is, however, pivotal that (i.e. stability) and cultural transmission (i.e. learning these epigenetic changes might be amenable to modifi- processes). cations. Adoption of pups of high-LG rats by mothers displaying the low-LG phenotype restore the normal Social Epigenetics stress response phenotype (Darnaude ´ ry et al., 2004). More recently, the maternal programing of stress McGuinness et al. (2012) reported the association response was shown to be reversible on administration between SES and global DNA-methylation in the of DNA-methylation modulator drugs (Weaver et al., pSoBid cohort, a study group with strong social health 2005). Although these results were so far obtained in gradients from the city of Glasgow. Specifically, they animal models, it should be clear how these findings found that vast hypomethylation was associated with might be relevant for researches who try to address the severe deprivation and being a manual worker. Also, environmental insults in early infancy. they observed a positive trend between number of In conclusion, the epidemiological evidence of years spent in education and global DNA-methylation. early programing and intergenerational transmission They independently tested the association of DNA- of metabolic and psychological conditions in humans methylation with CVDs and inflammation markers, is partly explained by epigenetic mechanisms, evidence finding that CVD risk is associated with hypomethyla- of which is strong in animal models. Through epigenetic tion when controlling for SES and lifestyle factors. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 146 LOI ET AL. Borghol et al. (2012) have investigated this question in 344). Responsibility-catering prioritarians attach moral further detail, by identifying specific epigenetic markers weight to redressing disadvantage for which people are linked to SES in the 1954 British Birth Cohort, which not responsible, but they also attach moral weight to were found to cluster in specific regions of the genome aiding the worse off, the more worse off they are. They linked to specific human functions (e.g. higher methy- judge social policy in terms of its aggregate utility out- lation, and thus repression, of sensory perception of come, but unlike traditional utilitarians, they attach smell and taste in low SES individuals). more weight to generating utility for worse off people In the next chapter, we will review some normative and if the disadvantage is due to bad luck. considerations that have been put forward to explain if, For luck-egalitarians of both types, there is no intrin- why and to what extent social inequalities are unjust and sic moral difference between a disadvantage that is a discuss whether the three features of social epigenetic deliberate or accidental effect of social institutions and traits induce any change in that ethical assessment of one produced by the genetic lottery. In education, for existing inequalities and the interpretation of the nor- instance, because no one is alleged to deserve innate mative principles themselves. In fact, social epigenetic natural talents, luck-egalitarians might favor investing traits are morally important because they may more resources in the education of the least-talented strengthen existing normative considerations (or sug- students, to close any sort of innate (e.g. genetic) gap. gest new moral issues) but also because they cut across But luck-egalitarians may also allow investing more re- traditional distinctions that have been used to express sources for the education of the most talented when it the normative principles themselves, as the difference maximizes the return of the investment, neutralizing the between acquired and innate features or between influence of arbitrary factors on outcomes ex post, i.e. social and natural traits. through taxation and redistribution: after redistribution, morally arbitrary factors (e.g. unequal talents at birth) ought not to engender unequal attainments in income Health Inequalities and Justice terms (Hild and Voorhoeve, 2004). A wide range of different, often irreconcilable, moral Notice, however, that income compensation is only views supports the view that health inequalities are im- second best from the viewpoint of the people affected portant for justice. Each view may provide a different by bad brute luck. It places its recipients in a passive explanation why health inequality, in itself, or when role, encouraging a pitiful attitude by others associated to social inequality, is unjust. In this article, (Anderson, 1999). It can hardly offset the lack of however, we shall focus on the relationship between social prestige, or the intrinsic self-realization rewards health and equality of opportunity and on the relation- (Rawls, 1999; Taylor, 2004), attached to desirable social ship between health and socially created inequalities. positions. Moreover, unequal power and responsibility The idea of equality of opportunity is interpreted differ- is a probable cause of the social gradient of illness and ently by different moral theories, concerning the rele- disease, independently of income (Brunner and vance for equality of opportunity of natural vs. social Marmot 2006). For this reason, it might be argued inequalities. that the first best solution should be correcting the So-called ‘luck’-egalitarians aim to equalize outcomes source of opportunity disadvantage at its outset, even due to natural inequalities. They hold that it is unfair to by intervening on the distribution of natural talents, suffer disadvantage from factors beyond one’s control, when feasible, through genetic technology and en- natural and social circumstances alike. Another version hancement (Hunter, 2012: 42; Segall, 2010). of the ‘luck-egalitarian’ idea invokes a ‘prioritarian’, By contrast, Rawlsian egalitarians think that equality rather than an ‘egalitarian’, rationale. According to of opportunity requires removing social sources of dis- prioritarianism, ‘one ought as a matter of justice to advantage. The ‘Fair Equality of Opportunity Principle’ aid the unfortunate, and the more badly off someone (henceforth FEO) requires the following: is, the more urgent is the moral imperative to aid’ assuming that there is a distribution of natural (Arneson 2000: 343). Thus, according to a prioritarian assets, those who are at the same level of talent version of luck-egalitarianism (or equivalently, a ‘re- and ability, and have the same willingness to use sponsibility-catering’ version of prioritarianism), ‘the them, should have the same prospects of success moral value of altering a state of affairs in a way that regardless of their initial place in the social makes someone better off or worse off depends, other system. [...] The expectations of those with the things being equal, on the degree of responsibility the same abilities and aspirations should not be person bears for her present condition’ (Arneson 2000: affected by their social class (Rawls, 1999: 63). Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 147 Notice that FEO does not require equal life chances for monitoring markers’, which provide an overall picture people whose natural endowments are not the same. of accumulated environmental insult and epigenetic risk This, one may argue, limits societal responsibilities to of disease. Imagine a society in which people can be correcting disadvantage due to poor access to education, informed by their family physician of the accumulation training, social networks and other social advantages. of risk factors due to specific environmental insults, Biological (dis)advantage should be classified as ‘un- including those arising prenatally and in early childhood equal natural assets’ and fall outside the scope of the for which people cannot be held responsible. principle. The difference between the luck-egalitarian There are at least two important ethical consequences and the Rawlsian conception of equality of opportunity of this gain of information. First, epigenetic monitors is, thus, that the luck-egalitarian aims at maximally might counterbalance currently skeptical views held by reducing the influence of morally arbitrary disadvan- the public of environmental risk, whereby individuals tage, natural and social alike, while the Rawlsian aims heavily exposed to risk do not develop disease and con- at neutralizing the impact of social background. stitute often cited exceptions to the statistical rule (e.g. In what follows, we discuss the relevance of DOHAD ‘he/she smoked 40 cigarettes per day and yet did not and epigenetics to these two conceptions of equality of develop lung cancer’). Consider a statistical risk factor, opportunity. such as ‘watching TV for 3 hours a day in childhood leads to greater asthma risk’ (Sherriff et al., 2009). Persuasion by statistical evidence will be greater if, Implications of Epigenetics for amongst the population at risk (e.g. ‘children watching Luck-Egalitarianism TV more than 3 hours a day’), epigenetics might aid in What are the implications of DOHAD and epigenetics identifying the population more likely to be affected by the environmental risk (‘children watching TV more for the luck-egalitarian way of considering equality of opportunity? We shall consider two possibilities. In than 3 hours a day with early epigenetic evidence of some cases, epigenetic traits may not be amenable to increased asthma risk’) as opposed to the overall popu- modification, at least given the present level of biomed- lation exposed. We have known for a long time that ical technological development. In others, they may be many diseases do not strike blindly, but follow from a amenable to modification, but the development of life-long accumulation of environmental insults, and therapies may require public investment. that people from disadvantaged social backgrounds are more likely to experience unfavorable environments Epigenetics as a risk monitor in their lifecourse too. But more precise epigenetic mar- kers may help convincing the public of the importance In this section, we discuss the luck-egalitarian implica- of these factors. tions of discovering epigenetic predispositions not The second is the possibility of direct applications. If amenable to modification. As shown in section in the future the epigenetic stratification of the disease, ‘Maternal diet and adult outset diseases predispos- within the same environmental risk group, will be pos- itions’, some disease risks are programed since concep- sible with a high degree of accuracy, it would develop a tion due to facts concerning the maternal environment. novel notion of ‘personalized risk’, whereby individuals Clearly no one can be considered responsible for disad- who are less affected by certain risks (e.g. watching TV), vantage accrued in this way. According to the luck- could indulge more in those risks without the potential egalitarian conception of equality of opportunity, justice guilt associated with those behaviors in the general requires compensation of brute luck disadvantage, e.g. population and without the negative health outcomes. prenatally advantaged people ought to subsidize the Moreover, the luck-egalitarian rationale of equality of health care costs of prenatally disadvantaged ones. opportunity justifies directing more resources for dis- However, it is known that different individuals react ease prevention to individuals who are at higher perso- to environmental insults to varying degrees (due to their nalized risk. This kind of prioritization seems justified genetic and physiological differences). Epigenetics based on a luck-egalitarian rationale, as among people might provide a measurable magnitude of the extent to which environmental insults have, indeed, caused making similar choices (watching TV more than 3 hours a day), some people are more unlucky than others, due harm in a person’s genome and thus cause predispos- ition to specific diseases, providing more accurate meas- to physiological (e.g. genetic) and environmental factors ures of disease risk due to environmental exposures. (e.g. disadvantaged social background) beyond their Epigenetic markers might thus become ‘health control. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 148 LOI ET AL. Notice that such information need not be made avail- greater impact on the health inequalities there are: able to the public in ways that threaten personal privacy there ought to be both less differences in health between and might expose the victims of bad natural luck to the equally prudent (or reckless) and more differences in further threats of discrimination. Access and utilization health between the prudent and the reckless. This would of sensitive medical records should be designed to maxi- indeed be the most plausible consequence of taking a mize the privacy and reduce the threat of discrimination certain ‘desert-based’ view of justice: justice is achieved against adult citizens. A properly designed system may when those who make the greatest sacrifices of enjoy- empower citizens to use morally relevant epigenetic ment and fun to protect their health enjoy comparably information to their own advantage (e.g. justify health better health than the rest. But this is not the way luck- care entitlements for people in high-risk categories), egalitarianism is standardly understood. Luck-egalitar- while reducing their own privacy risks. People may vol- ians favor removing inequalities for which individuals untarily undergo an array of tests and then be granted are not responsible, not promoting inequalities that some priority relative to health prevention and care. In reflect responsibility: they maintain that there ought to contrast to what private health insurance coverage be less differences between the equally prudent (or reck- less) but they are indifferent, or even favor minimizing would do, governments would be justified, for instance, in subsidizing the adult patient with asthma who, as inequality between the prudent and the reckless. a child, was in the highest risk group, for no fault of Finally, one potential implication of epigenetic testing his or her own. This would single out interventions is that it might be able to capture inherited initial dis- targeting specific groups, e.g. parentally neglected advantage deriving from environmental insults of earlier children with special physiological vulnerability to generations. If conclusive evidence is provided that environmental effects, as having some degree of priority social disadvantage is transmitted across generations over lower risk groups. through biological channels, more people will under- The availability of reliable indicators of early-life dis- stand the importance of meeting health care obligations advantage supports the duty to contribute to the health by restructuring social institutions more broadly than care of others as a matter of equality of opportunity, just health care. As emphasized by the literature on the understood along luck-egalitarian lines. But the point social determinants of health, social reforms for social could be made that testing negative does not equate mobility and reducing social inequalities at birth might straightforwardly with being responsible of increased have a greater aggregate impact on health than improv- health needs. Other bad circumstances could get wired ing individualized health care. Suppose that socioeco- in the body in a yet unknown or undetectable fashion. nomic inequalities affect the parental epigenome (as Even the most sophisticated predictive tools, including suggested by the evidence for epigenetic social stratifi- epigenetic and nonepigenetic indicators, only capture a cation discussed in ‘Social epigenetics’ section) and that limited amount of circumstances due to brute luck. inherited features give socially advantaged children a In response, the argument is not meant to weaken the better start in life (as suggested by the evidence of health care entitlements of those who are not demon- inter-generational transmission discussed in ‘Maternal strably responsible for their bad health. It may well be diet and adult outset diseases predispositions’ and irrelevant to societies that recognize a societal duty to ‘Parenting style and psychological conditions’ sections). meet citizen health needs unconditionally. But consider If so, achieving starting-gate equality of opportunity a society in which good health care and effective preven- requires tackling inequalities of outcomes affecting the tion is only for the people who can afford it, e.g. through parental epigenome in a heritable way. private insurance. Relative to this baseline, the above In conclusion, knowledge of epigenetic mechanisms proposed policy reduces the amount of morally may increase our ability to achieve (luck-egalitarian) arbitrary disadvantages. While leaving many morally equality of opportunity, by unraveling the mechanism arbitrary inequalities untouched, it still produces an through which the health prospects of a population are improvement from a luck-egalitarian point of view if affected by the unequal choices and circumstances of it contributes to equalizing health outcomes. their parents. (If epigenetics does not play an independ- Notice that we are imagining a public use of epigen- ent causal role, it will provide at least a reliable monitor etics to justify public policies aiming at improving of the impact.) Later on it will be pointed out that, to the health in the direction of health equality,or priority for extent that socioeconomic institutions play a causal role, the worst off. Someone may understand luck-egalitarian- there will be an overlap, in practice, between the luck- ism as the claim that a more just society would be one in egalitarian and Rawlsian conceptions of equality of which individual differences of responsibility have a opportunity concerning epigenetic disadvantage. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 149 phenomena, which is highly relevant in this respect: Reversible and preventable epigenetic traditional instruments of investment on human capital predispositions: correcting early might in fact arrive too late if the vulnerability to dis- disadvantage as investment eases is established very early on. An epidemiological Let us now turn to the hypothesis that epigenetic study (Feinstein, 2003) illustrates the establishment of changes be reversible. Recent data from both in vitro relative cognitive capabilities in UK children: these are and in vivo experiments show that early acquired highly associated with social status and independent epigenetic predispositions might be. As we saw in from baseline native levels but also determined soon section ‘Case-studies’, adverse health effects of early after birth and relatively unamenable to modification programing in rats (both nutrition and mothering on school entrance. This is challenging for policy makers style) can be reversed. Not only is the epigenome a ‘bio- because to obtain the same results that were previously sensor of exposure and/or outcome’ (Relton and Davey thought to be achievable through schooling, institutions Smith, 2012: 7) increasing our diagnostic abilities (in must be designed that reach infants at a young age, and ways that are relevant for justice) but it also opens up in fact, even the condition of the previous generation new avenues for innovative preventive interventions. ought to be tackled (Heckman, 2008). It might be possible to design environmental or When early investment in human capital and health pharmacological interventions for reverting the poten- of the population promotes economic and cultural tial adult consequences of a particular mothering style growth to a sufficient extent to repay the initial invest- at the molecular, cellular and physiological level. One ment, preventive policies should be supported as an implication of luck-egalitarianism is that there is a efficient, as well as fair, way to tackle disadvantage and prima face duty of justice to intervene: the possibility disease in the population. of reverting programed traits, when epigenetic informa- tion is a reliable biosensor, might efficiently prevent a Implications for Rawlsian Egalitarianism process of life-time accumulation of disadvantage that ends up in disease. The duty to develop and provide therapies and social This duty is only prima facie, meaning that on a tight policies to prevent the accumulation of epigenetic risk budget, resources may have to be diverted to meet more rests on the assumption that social justice requires cor- immediate priorities. But the importance for health recting the influence of causes of disadvantage for which justice of preventive measures should not be underesti- people are not responsible, natural and social alike. mated. True, health prevention competes for resources It might be objected that moderate egalitarians (e.g. with care for immediate health needs. But it can often be Rawls) are not committed to intervene in the distribu- both more efficient and just to prevent diseases, rather tion of the epigenetic predispositions people are born than cure them. In what follows, we shall present some with. It is only natural for the people favored by the considerations in support of the idea that acting on early natural (epi)genetic lottery to end up with better epigenetic determinants of diseases could be desirable health prospects. Those who are born with the worst from the point of view of efficiency. natural assets can at most expect society to design a Epigenetic disadvantage may matter in virtue of its tax system that redistributes wealth to their advantage. early onset. If one considers harm to a person in a life- They certainly cannot expect society to subsidize expen- course perspective, early disadvantage, even of milder sive medical services for the sake of correcting their quantity, may involve a large disutility in the long run. unequal life chances. This is clear in the ‘lifetime accumulation’ paradigm, in Against this objection, epigenetics forces us to recon- which genetic, epigenetic and socioeconomic determin- sider what counts as the natural/social boundary of ants of bad health reinforce each other, leading to a equality of opportunity. The paradigmatic social disad- continuous exposition to several drivers of diseases vantage, in Rawls, is class disadvantage, namely being and social exclusion. Any loss of realized ability due to born and growing, until maturity, in a family low in the adverse upbringing is considered to be a loss (in prod- hierarchy of income and power. Social disadvantage is uctivity force) and might even correlate with some social corrected by ensuring that all citizens, no matter their ‘bads’, such as socially expensive exclusion that society initial place in the social system, can access to education would necessarily have to tackle later on (Esping- and training that fits their natural predispositions. By Andersen, 2002; Heckman, 2008). contrast, the paradigmatic instance of natural disadvan- The idea of a crucial time window, in which early tage is the unequal distribution of genetic predispos- programing takes place, is a feature of social epigenetic itions, regarded as the outcome of a ‘natural lottery’. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 150 LOI ET AL. The metaphor of a ‘natural lottery’ is misleading in opportunity (e.g. everyone having access to the same the case of epigenetic traits that record environmental education or health care) is in theory compatible with impacts and are inter-generationally transmitted. outcome inequalities of any dimension. This assump- Consider an unfavorable predisposition to a common tion seems to be presupposed in the Rawlsian frame- disease that is (i) induced by childhood malnutrition works, where Fair Equality of Opportunity is distinct (‘Maternal diet and adult outset diseases predispos- from (and constrains) the Difference Principle, a prin- itions’ section) or maternal deprivation (‘Parenting ciple applying to the distribution of outcomes (income, style and psychological conditions’ section), (ii) highly wealth and the amount of power characteristic of every correlated with parental social disadvantage, (iii) trans- job and, more broadly, social position). The Difference mitted to the next generation. Grandchildren in a so- Principle permits all inequalities of income, wealth and cially disadvantaged family could inherit from their power that maximally benefit the worst off group in the socially disadvantaged parents and grandparents a population. Apparently, both Rawlsian equality of op- greater risk of metabolic disorders (‘Maternal diet and portunity and the Difference Principle are compatible adult outset diseases predispositions’ section), or stress with large socioeconomic inequalities: Fair Equality of responsitivity (‘Parenting style and psychological con- Opportunity allows all inequalities among the differ- ditions’ section). These are both ‘natural endowments’ ently talented and motivated, while the Difference and ‘socially generated’ endowments, partly explained Principle justifies unequal rewards for different jobs by social disadvantage produced by human institutions. (e.g. paying physicians and bank directors more than Even if a society where FEO is implemented subsidizes manual workers) when needed to attract more talented early health care and education, it may leave inherited and motivated people to perform the most difficult and epigenetic disadvantage untouched. challenging jobs, if this contributes to improving the On a restrictive interpretation of FEO, these inherited expectations of the least advantaged. Suppose that a differences are natural endowments because they are change in workplace hierarchies, e.g. an increase of dis- innate. Hence, FEO does not require financing medical ciplinary powers for managers, improves the annual treatments or social policies that can revert them or income of subordinate workers by 1000 E, while at prevent them from causing further disadvantage. But a the same time inducing in them a stress-related increase different, more extensive interpretation of FEO is at least in smoking behavior and the consumption of fatty food. equally plausible. The biological disadvantage of the Let us also imagine that this produces epigenetic grandchild is produced by adverse social conditions changes, which are passed to the next generation, so experienced by parents and grandparents. So it can be that at birth the children of subordinates are at greater described as an effect of the starting position in soci- risk of metabolic disease than the children of managers. ety, just as the paradigmatic form of opportunity in- In other words, there is a trade off between greater equality FEO is concerned with, namely unequal income expectations for generation N and more equal access to education. If required to promote equality of opportunities with respect to health for generation opportunity, a liberal state may legitimately attempt to N+ 1. In the Rawlsian theory, FEO constrains (being correct epigenetically inherited disadvantage by subsi- ‘lexically prior’ to) the application of the Difference dizing special interventions, just as it attempts to ‘level Principle. Thus, when these circumstances obtain, the the playing field’ by subsidizing the education of the lexical priority of the FEO represents an objection poor. against conferring more authority to managers to con- As pointed out in section ‘Reversible and preventable trol subordinates, otherwise permitted by the Difference epigenetic predispositions: correcting early disadvan- Principle. On the strict interpretation of FEO, this con- tage as investment’, this may take the form of designing straint is not justified: it does not affect the ‘expectations pharmacological or lifestyle correctives for reverting of those with the same abilities and aspirations’, but only programed phenotypes that are epigenetically measur- the expectations of people born with different natural able. But it is perhaps even more interesting to point out (epigenetic) endowments. On the broad interpretation, the consequences of the Rawlsian view, so interpreted, if FEO commits society to ensure that the expectations of epigenetic imprinting is not reversible. Paradoxically, individuals ‘should not be affected by their social class’, epigenetic inheritance could entail that equality of op- including when social class operates via natural endow- portunity can only be achieved by achieving a more ments, so it places limits to outcome inequalities in one equal distribution of outcomes. The ideal of equality of opportunity is usually put forward as an alternative generation for the sake of achieving more equal starting to the ideal of equality of outcome because equality of positions in the next. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 151 conception by parental donation of developmental Conclusions material: also environmental clues might program Our discussion of luck-egalitarian and Rawlsian equality adult traits (i.e. early in development or in utero) and of opportunity in light of epigenetic discoveries leads us their intergenerational similarities, i.e. if parents and their offspring share the developmental environment; to three broad conclusions that might be relevant to (iii) it suggests that biological inheritance is reversible public health: through environmental clues and thus influences by social structure. If we are to retain a distinction between (1) Epigenetics can be considered a biomarker of natural lottery and acquired traits we must explain how brute-luck disadvantage: Epigenetic screening it may fit this updated picture of social and biological might diagnose early-life and inherited insults due inheritance. Also, if we want to use that distinction in to factors beyond personal control, thus giving moral theory, we must explain why—if at all—the dis- people reasons to demand the provision of health tinction between biologically and socially determined services as a matter of equality of opportunity. traits retains its moral weight when transferred in the (2) Reversibility of programed phenotypes: The ad- new view suggested by DOHaD and epigenetics verse effects of inherited or early-life insults on findings. health measurable through the epigenome might While it is important to bear in mind the distinction be reversible through early pharmacological thera- between a Rawlsian and a luck-egalitarian approach, pies or environmental interventions, avoiding on the issue of correcting for (social) epigenetic disad- brute-luck health inequalities that are harder to vantage a significant convergence between the two tackle later on. approaches obtains. While the social circumstances (3) Nature vs. nurture: The social determination of experienced by our parents and grandparents have no epigenetic traits that can be inherited shows that direct influence on the distribution of genotypes (save innate traits are not necessarily insensitive to social from mating patterns, with which, however, a liberal structures. Reasons to tackle epigenetic disadvan- state cannot interfere), they may have a more direct in- tage, being an instance of inherited social disadvan- fluence on epigenetic predispositions. But if epigenetic tage, are also offered by the more restrictive traits are responsive to environmental cues, they can be Rawlsian version of equality of opportunity. influenced by social policy, and there is a fuzzy bound- ary between controversial ‘biopolitics’ (e.g. genetic en- More generally, it makes a significant difference hancement) and traditional social policy focused on the whether the natural inequalities mentioned by the main socioeconomic institutions (e.g. redistributive Rawlsian theory are identified with different genotypes taxation, access to education) in the Rawlsian tradition. or different epigenetic traits. Epigenetic channels of It is thus imperative from the point of view of public inheritance challenge the received view on the distinc- health and equality of opportunity to explore how the tion between social and biological inheritance of advan- different ways of conceptualizing this boundary affect tages and disadvantages. That view is based on what has direction of scientific enquiry, ethical views and policy been called the DNA-centric donation/conception theory development. of inheritance of features (Mameli, 2005): it explains bio- logical similarities between parents and their offspring through the donation at conception of a privileged de- Conflict of Interest velopmental material, DNA, while it leaves to cultural None declared. channels of transmission between parents and their offspring any other forms of similarity between them. The idea of the ‘natural lottery’ relies on that received Author Contributions view: traits that are explained by the donation of DNA at conception are due to the natural lottery, all the others All authors contributed equally to the design and con- are instead due to social structures. Epigenetics compli- ceptualisation of this article. Michele Loi and Lorenzo cates the picture in two ways: (i) it expands the list of del Savio wrote the sections ‘Introduction’ and ‘Health developmentally privileged material that can be passed Inequalities and Justice’. Lorenzo del Savio and Elia on at conception from parents to their offspring Stupka wrote ‘Epigenetics and Health Inequalities’. All (e.g. patterns of DNA-methylation); (ii) it suggests authors revised the whole manuscript and wrote the that biological inheritance does not happen only at section ‘Conclusion’. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 152 LOI ET AL. Champagne, F. (2008). Epigenetic Mechanisms and the Notes Transgenerational Effects of Maternal Care. Frontiers 1. Other influential theories start from an explicit ex- in Neuroendocrinology, 29, 386–397. Chmurzynska, A. (2010). 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Social Epigenetics and Equality of Opportunity

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Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 PUBLIC HEALTH ETHICS VOLUME 6 NUMBER 2 2013 142–153 142 Social Epigenetics and Equality of Opportunity Michele Loi , Center for Translational Genomics and Bioinformatics, CEHUM, Universidade Do Minho and San Raffaele Scientific Institute Lorenzo Del Savio, Istituto Europeo di Oncologia Elia Stupka, Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute Corresponding author: Michele Loi, Centro de Estudos Humanı´sticos, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Tel.: (+39) 320 027 3272; Email: loi.michele@ilch.uminho.pt Recent epidemiological reports of associations between socioeconomic status and epigenetic markers that predict vulnerability to diseases are bringing to light substantial biological effects of social inequalities. Here, we start the discussion of the moral consequences of these findings. We firstly highlight their explanatory importance in the context of the research program on the Developmental Origins of Health and Disease (DOHaD) and the social determinants of health. In the second section, we review some theories of the moral status of health inequalities. Rather than a complete outline of the debate, we single out those theories that rest on the principle of equality of opportunity and analyze the consequences of DOHaD and epigenetics for these particular conceptions of justice. We argue that DOHaD and epigenetics reshape the conceptual distinction between natural and acquired traits on which these theories rely and might provide important policy tools to tackle unjust distributions of health. As we explain at length below, epigenetics is defined Introduction as the study of the inheritance (between cells and/or In this article, we assess the implications for justice and organisms) of traits (gene expression or phenotypes) health of the developmental origins of health and without changes to the underlying DNA sequence. As disease (DOHaD) hypothesis and findings in epigenetics we shall indicate, there are three features of epigenetic that corroborate it. Other articles have addressed traits that make them important for a normative analysis the ethical and social consequences of epigenetics of health inequalities: (Rothstein et al., 2009; Drake and Liu, 2010; Hedlund, 2012), arguing that the fight against epigenetically  Sensitivity to social structures: Some epigenetic transmitted forms of disadvantage is more a political phenomena are highly responsive to environmental than an individual responsibility. In this essay, we changes, which are affected by social institutions. discuss the scientific evidence on which this claim is  Early programing: Several epigenetic traits are based and defend a case for public health interventions established early-on in development, and their effects based on epigenetic discoveries in a framework of on health unfold throughout the life course. equality of opportunity. Because the concept of equality  Trans-generational transmission: There is evidence of opportunity is interpreted in different ways by differ- in both animal models and epidemiological ent moral traditions, we analyze the luck-egalitarian and studies that epigenetic traits can be trans- the Rawlsian versions showing that the two overlaps generationally inherited. In addition to genetic significantly in this context. inheritance that provides adaptive flexibility in Recent discoveries in epigenetics improve our under- the long (evolutionary) time span, epigenetics standing of how individual health and therefore oppor- constitutes other, semi-stable, biological mechan- tunity is affected by early developmental events and isms through which features are inherited previous generations’ environmental circumstances. through generations. doi:10.1093/phe/pht019 ! The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 143 In virtue of the three features above, epigenetics mechanistic base of developmental programing? provides a chain of connections between what used to Epigenetics, the study of mitotically (or meiotically) be qualified as social and natural inequality, leading to a heritable changes that alter gene expression and pheno- reformulation of these contested boundaries. This also types, but are independent from the underlying DNA leads to a rethinking of the time-frame and scope of sequence, can provide some answer to this important equality of opportunity. question (Gluckman et al., 2008). Epigenetics is the study of semi-stable molecular states (e.g. life long and transmissible over a limited number of generations) that Epigenetics and Health influence physiology in subtle ways during develop- Inequalities ment, in physiological conditions and in the establish- ment of several diseases. Also, they are sensitive We begin this review of the public health implications of to environmental clues rather than being exclusively epigenetics by situating a discussion of epigenetic mech- endogenously determined and provide biological anisms into the broader context of the social determin- systems with flexibility, the capability to respond to ants of health inequalities. environmental challenge and rudimentary ‘learning’ The incidence of several diseases is negatively corre- mechanisms. Both stability and sensitivity to the envir- lated with socioeconomic status (SES), as measured by onment are features that render epigenetics an eligible income, wealth and educational level and independently mechanistic explanation of early programing. from the universal public provision of health services. Indeed it is this semi-stability or relative stability to This striking epidemiological phenomenon is illustrated confer such a pivotal role to epigenetics in a revised by the city of Glasgow, UK, where people in the poorest understanding of natural traits and response to envir- neighborhoods expect to live 12 years less than their onment. Indeed, epigenetic biological phenomena are counterparts in the richest parts of the city. Poverty ex- slower than continuous dynamic gene expression plains only part of these disparities: a steady gradient of changes affecting cells and organisms in their daily health outcomes across social classes has been observed lives, yet faster than genetic inheritance and fitness, for many conditions, even among groups that are fully which occur at a slow pace over a large number of gen- above the threshold of poverty (Marmot, 2005). erations. At the same time they are able to respond to Neither the steepness of the health gradient nor the sustained environmental stimuli, and can be inherited magnitude of these disparities can be accounted for by through several, but possibly not many, generations. the social stratification of a single kind of risk factor. These characteristics taken together place epigenetics Rather, material (e.g. poverty), behavioral (e.g. diet), in a unique position in reshaping our understanding biological (e.g. blood pressure) and psychosocial (e.g. of how natural traits, traditionally viewed as heritable stress) pathways may add up and interact to establish traits selected through countless generations during social health inequalities (Arendt and Lauridsen, 2007; evolution, might actually evolve in a more dynamic Blane, 2006). manner as a response to environment, and thus, in the In our review we focus on the early life effects of SES. case of humans, to social environments. In ‘DOHaD and epigenetics’ section, we introduce the The paradigmatic epigenetic phenomenon, in concept of ‘DOHaD’, the role of epigenetics as a mech- fact one that has been discovered early on, is DNA- anism for DOHaD, and for the inheritance of acquired methylation, the addition of a methyl group to a DNA predispositions (in a quasi-Lamarkian fashion). In cytosine residue, initially thought to occur mostly at ‘Case-studies’ section, we discuss two specific cases in cytosine-guanosine dinucleotides (CpGs) in promoter more detail: nutrition and parenting style, associated, regions of genes, but now understood to be a more respectively, with metabolic diseases and psychological widespread phenomenon occurring throughout the conditions. In section ‘Social epigenetics’, we provide genome also at non-CpG nucleotides (in embryonic some evidence of the social stratification of epigenetic stem cells) and away from promoters (in intergenic differences between individuals. regions). Changes in the DNA-methylation patterns at the genomic level are involved in the regulatory control DOHaD and epigenetics of gene expression in mammalian development and in The concept of ‘DOHAD’ has been introduced to the development of several human physiological traits describe exogenous influences on early development as well as diseases. This epigenetic modification has its that may predispose the organism toward specific own control machinery, a set of enzymes (DNA methyl phenotypes or diseases (Barker, 1995). Which is the transferases), which generate de novo methylation Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 144 LOI ET AL. patterns, as well as controlling the maintenance of adaptive if food scarcity is endemic, but becomes ‘mal- DNA-methylation patterns throughout development. adaptive’ when it matches poorly an environment where Although in mammals DNA-methylation is repro- there is plenty of high-energy foods. Similarly, a high-fat gramed in the earliest phases of development (first maternal diet programs her offspring for increased risk days after conception around the time of in utero of adult obesity or metabolic disorders in childhood implantation of the embryo), there is evidence of (Chmurzynska, 2010). Both these mechanisms may be trans-generational persistence of DNA-methylation relevant for the early-programing hypothesis in life- signatures (i.e. imprinting), which are also involved in course social epidemiology, in fact in two different the development of certain developmental conditions. contexts of sharp disparities in health outcomes. The Recent advances in sequencing techniques (i.e. association between early undernourishment and meta- next-generation sequencing) rendered possible the bolic disorders may explain the sharp increase in the high-throughput screening of genome-wide DNA- prevalence of the latter in emerging economies, which methylation patterns, thus providing the first genome- in fact experience a ‘double-burden’ of diet-related con- wide maps that will allow us to correlate molecular ditions (Popki, 2001). The association between maternal differences at the epigenetic level and significant health hypernutrition and children conditions is instead im- parameters, such as the susceptibility to cardiovascular portant in high-income countries, where obesity is so- diseases (CVDs). Thanks to next-generation sequencing, cially stratified and especially so among women: aside we are now also able to explore in a more complete from behavioral channels of transmission of childhood manner other types of epigenetic signatures beyond obesity, which is predicted by parental body max index, DNA-methylation, i.e. those based on histone modifica- programing may be partially responsible of this ‘inher- tions (histone methylation, acetylation, etc). The itance’ of the condition (Sullivan et al., 2011). number of modifiable histones, and the number of Epidemiological studies have also begun indicating modifications observed so far have brought the scientific intergenerational transmission of DOHAD effects (i.e. community to point to a ‘histone code’ because of observing a grandfather to grandson DOHAD effect) its potential complexity. Nonetheless histone modifica- (Kaati et al., 2007). These have been investigated in tions have already been shown to be involved in greater depth and across more generations in animal epigenetic inheritance and epigenetic control of gene models. A study of a low-protein diet in rats, for ex- expression. ample, has indicated that the phenotypic effects of the In conclusion, epigenetic mechanisms appear to be diet given to the so-called F0 generation (i.e. the first set involved in the early programing of adult phenotypes of parents from which the experiment starts) are indeed and the transmission of molecular phenotypes across observed not only in the F1 (i.e. in their children), but generations. In the next section, we will discuss the also in the F2 (i.e. their grandchildren) and finally the empirical evidence bearing on two classes of cases: meta- phenotype is lost in the F3, underlining the semi-stable bolic disorders and psychological conditions. heritable behavior of this programing effect (Harrison and Evans, 2009). Moreover, it was shown that the effects on hypertension of low-protein diet during fetal life were Case-Studies reversed on administration of pharmacological com- Maternal diet and adult outset diseases pounds blocking maternal glucocorticoid synthesis predispositions (Langley-Evans, 1997). Both the human cohorts and A paradigmatic case of the relevance of epigenetic animal models have been investigated in terms of the programing for adulthood diseases is nutrition during potential epigenetic mechanisms involved in the pregnancy (Sullivan et al., 2011). Subtler features of diets DOHAD effect providing early clues to the role of may program the newborn for conditions that will be DNA-methylation (reviewed in Mathers et al., 2010). visible only in adulthood. Both undernourishment and Parenting style and psychological conditions hypernutrition have been proposed to be influences of this kind. As for the former, in the studies of the popu- Health is important in its own right as for life opportu- lation affected by the 1944–45 Dutch famine maternal nities. Also, poor health is associated with lower educa- undernourishment was shown to be a predictor of tional attainments and therefore health is partly susceptibility to type II diabetes. Based on this, Neel responsible for the association between being born in (1962) proposed that maternal malnutrition may act as a poorer family and lower educational achievements an environmental switch that turns the metabolic system (Case et al., 2005). The latter are a crucial predictor of of the developing fetus in a thrifty mode, which is employment status and income, and therefore health Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 145 does impinge on opportunities in at least two ways: mechanisms, environmental insults in early infancy may directly and through educational careers. program future metabolic and psychological pheno- Moreover, there is a broader class of conditions that types later in life (DOHaD); moreover, environmental are certainly relevant for life opportunities and for insults experienced by parents and grandfathers can which epigenetic mechanisms might be responsible as be transmitted to children and grandchildren (inter- well: psychological conditions. In particular, stress generational inheritance). responsivity, cognitive ability and response to reward Evidence of direct inheritance is still sparse and open are highly sensible to early-life events, especially mater- to empirical scrutiny (Daxinger and Whitelaw, 2010). nal care (Champagne, 2008). Because these are also On the other hand, early programing could represent an features that will influence opportunities, recent discov- indirect way in which health disadvantages are acquired eries on the biology of early life circumstances and and passed on from parents to children. This inter-gen- psychological conditions might open up new policy erational stability of certain conditions is already known avenues to tackle disadvantages. in social epidemiology at the statistical level. Behavioral This DOHAD effect has also been furthered by and socio-structural channels of inheritance may ac- experiments with animal models. A study on rats’ count for this stability: children from poor backgrounds mothering styles gave some hints about how this might encounter social environments that are similar to their work (Weaver et al., 2004): the stress response mechan- parents’ and learning is a major pathway of inheritance ism is tuned by maternal behavior in early life and it also of unhealthy lifestyles. Jablonka and Lamb (2005) expli- leads to permanent changes in DNA-methylation and citly juxtaposed epigenetics and ‘cultural’ inheritance, histone acetylation of genes that are involved in stress fleshing out an analogy based on their inter- and response. The main idea beyond the discovery is that intra-generational stability and their sensitivity to maternal parenting style changes profoundly the physi- exogenous clues. Their ideas include the hypothesis ology of the rat pups, triggering a cascade of molecular that there could be more channels over and above cul- events that get written on their epigenetic code thus tural inheritance (e.g. learning) and genetics that explain modulating gene expression in adulthood. The re- how traits are inherited from parents to their offspring: searchers studied a phenotype of mothering behavior, in particular, epigenetics mechanisms would be sensitive frequent licking and grooming (high-LG), that was asso- to environmental clues, similarly to what happens in the ciated with high level of hippocampal glucocorticoid case of learning, while being at the same time relatively receptor activity, which is related to stress response. stable through time, as in the case of genetics. Their Because upregulated stress response is in turn asso- hypothesis replaces the distinction between innate bio- ciated with high-LG mothering style in adulthood, the logical traits and flexible learned traits with a continuum study provided the description of an epigenetic trans- of biological traits that are more or less programable by generational inheritance of a behavioral trait (Sapolsky, environmental clues and reprogramable by post hoc 2004). For our purposes (see section ‘Reversible and interventions. Epigenetics is thus a sui generis channel preventable epigenetic predispositions: correcting early of inheritance, which shares features both with genetics disadvantage as investment’) it is, however, pivotal that (i.e. stability) and cultural transmission (i.e. learning these epigenetic changes might be amenable to modifi- processes). cations. Adoption of pups of high-LG rats by mothers displaying the low-LG phenotype restore the normal Social Epigenetics stress response phenotype (Darnaude ´ ry et al., 2004). More recently, the maternal programing of stress McGuinness et al. (2012) reported the association response was shown to be reversible on administration between SES and global DNA-methylation in the of DNA-methylation modulator drugs (Weaver et al., pSoBid cohort, a study group with strong social health 2005). Although these results were so far obtained in gradients from the city of Glasgow. Specifically, they animal models, it should be clear how these findings found that vast hypomethylation was associated with might be relevant for researches who try to address the severe deprivation and being a manual worker. Also, environmental insults in early infancy. they observed a positive trend between number of In conclusion, the epidemiological evidence of years spent in education and global DNA-methylation. early programing and intergenerational transmission They independently tested the association of DNA- of metabolic and psychological conditions in humans methylation with CVDs and inflammation markers, is partly explained by epigenetic mechanisms, evidence finding that CVD risk is associated with hypomethyla- of which is strong in animal models. Through epigenetic tion when controlling for SES and lifestyle factors. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 146 LOI ET AL. Borghol et al. (2012) have investigated this question in 344). Responsibility-catering prioritarians attach moral further detail, by identifying specific epigenetic markers weight to redressing disadvantage for which people are linked to SES in the 1954 British Birth Cohort, which not responsible, but they also attach moral weight to were found to cluster in specific regions of the genome aiding the worse off, the more worse off they are. They linked to specific human functions (e.g. higher methy- judge social policy in terms of its aggregate utility out- lation, and thus repression, of sensory perception of come, but unlike traditional utilitarians, they attach smell and taste in low SES individuals). more weight to generating utility for worse off people In the next chapter, we will review some normative and if the disadvantage is due to bad luck. considerations that have been put forward to explain if, For luck-egalitarians of both types, there is no intrin- why and to what extent social inequalities are unjust and sic moral difference between a disadvantage that is a discuss whether the three features of social epigenetic deliberate or accidental effect of social institutions and traits induce any change in that ethical assessment of one produced by the genetic lottery. In education, for existing inequalities and the interpretation of the nor- instance, because no one is alleged to deserve innate mative principles themselves. In fact, social epigenetic natural talents, luck-egalitarians might favor investing traits are morally important because they may more resources in the education of the least-talented strengthen existing normative considerations (or sug- students, to close any sort of innate (e.g. genetic) gap. gest new moral issues) but also because they cut across But luck-egalitarians may also allow investing more re- traditional distinctions that have been used to express sources for the education of the most talented when it the normative principles themselves, as the difference maximizes the return of the investment, neutralizing the between acquired and innate features or between influence of arbitrary factors on outcomes ex post, i.e. social and natural traits. through taxation and redistribution: after redistribution, morally arbitrary factors (e.g. unequal talents at birth) ought not to engender unequal attainments in income Health Inequalities and Justice terms (Hild and Voorhoeve, 2004). A wide range of different, often irreconcilable, moral Notice, however, that income compensation is only views supports the view that health inequalities are im- second best from the viewpoint of the people affected portant for justice. Each view may provide a different by bad brute luck. It places its recipients in a passive explanation why health inequality, in itself, or when role, encouraging a pitiful attitude by others associated to social inequality, is unjust. In this article, (Anderson, 1999). It can hardly offset the lack of however, we shall focus on the relationship between social prestige, or the intrinsic self-realization rewards health and equality of opportunity and on the relation- (Rawls, 1999; Taylor, 2004), attached to desirable social ship between health and socially created inequalities. positions. Moreover, unequal power and responsibility The idea of equality of opportunity is interpreted differ- is a probable cause of the social gradient of illness and ently by different moral theories, concerning the rele- disease, independently of income (Brunner and vance for equality of opportunity of natural vs. social Marmot 2006). For this reason, it might be argued inequalities. that the first best solution should be correcting the So-called ‘luck’-egalitarians aim to equalize outcomes source of opportunity disadvantage at its outset, even due to natural inequalities. They hold that it is unfair to by intervening on the distribution of natural talents, suffer disadvantage from factors beyond one’s control, when feasible, through genetic technology and en- natural and social circumstances alike. Another version hancement (Hunter, 2012: 42; Segall, 2010). of the ‘luck-egalitarian’ idea invokes a ‘prioritarian’, By contrast, Rawlsian egalitarians think that equality rather than an ‘egalitarian’, rationale. According to of opportunity requires removing social sources of dis- prioritarianism, ‘one ought as a matter of justice to advantage. The ‘Fair Equality of Opportunity Principle’ aid the unfortunate, and the more badly off someone (henceforth FEO) requires the following: is, the more urgent is the moral imperative to aid’ assuming that there is a distribution of natural (Arneson 2000: 343). Thus, according to a prioritarian assets, those who are at the same level of talent version of luck-egalitarianism (or equivalently, a ‘re- and ability, and have the same willingness to use sponsibility-catering’ version of prioritarianism), ‘the them, should have the same prospects of success moral value of altering a state of affairs in a way that regardless of their initial place in the social makes someone better off or worse off depends, other system. [...] The expectations of those with the things being equal, on the degree of responsibility the same abilities and aspirations should not be person bears for her present condition’ (Arneson 2000: affected by their social class (Rawls, 1999: 63). Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 147 Notice that FEO does not require equal life chances for monitoring markers’, which provide an overall picture people whose natural endowments are not the same. of accumulated environmental insult and epigenetic risk This, one may argue, limits societal responsibilities to of disease. Imagine a society in which people can be correcting disadvantage due to poor access to education, informed by their family physician of the accumulation training, social networks and other social advantages. of risk factors due to specific environmental insults, Biological (dis)advantage should be classified as ‘un- including those arising prenatally and in early childhood equal natural assets’ and fall outside the scope of the for which people cannot be held responsible. principle. The difference between the luck-egalitarian There are at least two important ethical consequences and the Rawlsian conception of equality of opportunity of this gain of information. First, epigenetic monitors is, thus, that the luck-egalitarian aims at maximally might counterbalance currently skeptical views held by reducing the influence of morally arbitrary disadvan- the public of environmental risk, whereby individuals tage, natural and social alike, while the Rawlsian aims heavily exposed to risk do not develop disease and con- at neutralizing the impact of social background. stitute often cited exceptions to the statistical rule (e.g. In what follows, we discuss the relevance of DOHAD ‘he/she smoked 40 cigarettes per day and yet did not and epigenetics to these two conceptions of equality of develop lung cancer’). Consider a statistical risk factor, opportunity. such as ‘watching TV for 3 hours a day in childhood leads to greater asthma risk’ (Sherriff et al., 2009). Persuasion by statistical evidence will be greater if, Implications of Epigenetics for amongst the population at risk (e.g. ‘children watching Luck-Egalitarianism TV more than 3 hours a day’), epigenetics might aid in What are the implications of DOHAD and epigenetics identifying the population more likely to be affected by the environmental risk (‘children watching TV more for the luck-egalitarian way of considering equality of opportunity? We shall consider two possibilities. In than 3 hours a day with early epigenetic evidence of some cases, epigenetic traits may not be amenable to increased asthma risk’) as opposed to the overall popu- modification, at least given the present level of biomed- lation exposed. We have known for a long time that ical technological development. In others, they may be many diseases do not strike blindly, but follow from a amenable to modification, but the development of life-long accumulation of environmental insults, and therapies may require public investment. that people from disadvantaged social backgrounds are more likely to experience unfavorable environments Epigenetics as a risk monitor in their lifecourse too. But more precise epigenetic mar- kers may help convincing the public of the importance In this section, we discuss the luck-egalitarian implica- of these factors. tions of discovering epigenetic predispositions not The second is the possibility of direct applications. If amenable to modification. As shown in section in the future the epigenetic stratification of the disease, ‘Maternal diet and adult outset diseases predispos- within the same environmental risk group, will be pos- itions’, some disease risks are programed since concep- sible with a high degree of accuracy, it would develop a tion due to facts concerning the maternal environment. novel notion of ‘personalized risk’, whereby individuals Clearly no one can be considered responsible for disad- who are less affected by certain risks (e.g. watching TV), vantage accrued in this way. According to the luck- could indulge more in those risks without the potential egalitarian conception of equality of opportunity, justice guilt associated with those behaviors in the general requires compensation of brute luck disadvantage, e.g. population and without the negative health outcomes. prenatally advantaged people ought to subsidize the Moreover, the luck-egalitarian rationale of equality of health care costs of prenatally disadvantaged ones. opportunity justifies directing more resources for dis- However, it is known that different individuals react ease prevention to individuals who are at higher perso- to environmental insults to varying degrees (due to their nalized risk. This kind of prioritization seems justified genetic and physiological differences). Epigenetics based on a luck-egalitarian rationale, as among people might provide a measurable magnitude of the extent to which environmental insults have, indeed, caused making similar choices (watching TV more than 3 hours a day), some people are more unlucky than others, due harm in a person’s genome and thus cause predispos- ition to specific diseases, providing more accurate meas- to physiological (e.g. genetic) and environmental factors ures of disease risk due to environmental exposures. (e.g. disadvantaged social background) beyond their Epigenetic markers might thus become ‘health control. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 148 LOI ET AL. Notice that such information need not be made avail- greater impact on the health inequalities there are: able to the public in ways that threaten personal privacy there ought to be both less differences in health between and might expose the victims of bad natural luck to the equally prudent (or reckless) and more differences in further threats of discrimination. Access and utilization health between the prudent and the reckless. This would of sensitive medical records should be designed to maxi- indeed be the most plausible consequence of taking a mize the privacy and reduce the threat of discrimination certain ‘desert-based’ view of justice: justice is achieved against adult citizens. A properly designed system may when those who make the greatest sacrifices of enjoy- empower citizens to use morally relevant epigenetic ment and fun to protect their health enjoy comparably information to their own advantage (e.g. justify health better health than the rest. But this is not the way luck- care entitlements for people in high-risk categories), egalitarianism is standardly understood. Luck-egalitar- while reducing their own privacy risks. People may vol- ians favor removing inequalities for which individuals untarily undergo an array of tests and then be granted are not responsible, not promoting inequalities that some priority relative to health prevention and care. In reflect responsibility: they maintain that there ought to contrast to what private health insurance coverage be less differences between the equally prudent (or reck- less) but they are indifferent, or even favor minimizing would do, governments would be justified, for instance, in subsidizing the adult patient with asthma who, as inequality between the prudent and the reckless. a child, was in the highest risk group, for no fault of Finally, one potential implication of epigenetic testing his or her own. This would single out interventions is that it might be able to capture inherited initial dis- targeting specific groups, e.g. parentally neglected advantage deriving from environmental insults of earlier children with special physiological vulnerability to generations. If conclusive evidence is provided that environmental effects, as having some degree of priority social disadvantage is transmitted across generations over lower risk groups. through biological channels, more people will under- The availability of reliable indicators of early-life dis- stand the importance of meeting health care obligations advantage supports the duty to contribute to the health by restructuring social institutions more broadly than care of others as a matter of equality of opportunity, just health care. As emphasized by the literature on the understood along luck-egalitarian lines. But the point social determinants of health, social reforms for social could be made that testing negative does not equate mobility and reducing social inequalities at birth might straightforwardly with being responsible of increased have a greater aggregate impact on health than improv- health needs. Other bad circumstances could get wired ing individualized health care. Suppose that socioeco- in the body in a yet unknown or undetectable fashion. nomic inequalities affect the parental epigenome (as Even the most sophisticated predictive tools, including suggested by the evidence for epigenetic social stratifi- epigenetic and nonepigenetic indicators, only capture a cation discussed in ‘Social epigenetics’ section) and that limited amount of circumstances due to brute luck. inherited features give socially advantaged children a In response, the argument is not meant to weaken the better start in life (as suggested by the evidence of health care entitlements of those who are not demon- inter-generational transmission discussed in ‘Maternal strably responsible for their bad health. It may well be diet and adult outset diseases predispositions’ and irrelevant to societies that recognize a societal duty to ‘Parenting style and psychological conditions’ sections). meet citizen health needs unconditionally. But consider If so, achieving starting-gate equality of opportunity a society in which good health care and effective preven- requires tackling inequalities of outcomes affecting the tion is only for the people who can afford it, e.g. through parental epigenome in a heritable way. private insurance. Relative to this baseline, the above In conclusion, knowledge of epigenetic mechanisms proposed policy reduces the amount of morally may increase our ability to achieve (luck-egalitarian) arbitrary disadvantages. While leaving many morally equality of opportunity, by unraveling the mechanism arbitrary inequalities untouched, it still produces an through which the health prospects of a population are improvement from a luck-egalitarian point of view if affected by the unequal choices and circumstances of it contributes to equalizing health outcomes. their parents. (If epigenetics does not play an independ- Notice that we are imagining a public use of epigen- ent causal role, it will provide at least a reliable monitor etics to justify public policies aiming at improving of the impact.) Later on it will be pointed out that, to the health in the direction of health equality,or priority for extent that socioeconomic institutions play a causal role, the worst off. Someone may understand luck-egalitarian- there will be an overlap, in practice, between the luck- ism as the claim that a more just society would be one in egalitarian and Rawlsian conceptions of equality of which individual differences of responsibility have a opportunity concerning epigenetic disadvantage. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 149 phenomena, which is highly relevant in this respect: Reversible and preventable epigenetic traditional instruments of investment on human capital predispositions: correcting early might in fact arrive too late if the vulnerability to dis- disadvantage as investment eases is established very early on. An epidemiological Let us now turn to the hypothesis that epigenetic study (Feinstein, 2003) illustrates the establishment of changes be reversible. Recent data from both in vitro relative cognitive capabilities in UK children: these are and in vivo experiments show that early acquired highly associated with social status and independent epigenetic predispositions might be. As we saw in from baseline native levels but also determined soon section ‘Case-studies’, adverse health effects of early after birth and relatively unamenable to modification programing in rats (both nutrition and mothering on school entrance. This is challenging for policy makers style) can be reversed. Not only is the epigenome a ‘bio- because to obtain the same results that were previously sensor of exposure and/or outcome’ (Relton and Davey thought to be achievable through schooling, institutions Smith, 2012: 7) increasing our diagnostic abilities (in must be designed that reach infants at a young age, and ways that are relevant for justice) but it also opens up in fact, even the condition of the previous generation new avenues for innovative preventive interventions. ought to be tackled (Heckman, 2008). It might be possible to design environmental or When early investment in human capital and health pharmacological interventions for reverting the poten- of the population promotes economic and cultural tial adult consequences of a particular mothering style growth to a sufficient extent to repay the initial invest- at the molecular, cellular and physiological level. One ment, preventive policies should be supported as an implication of luck-egalitarianism is that there is a efficient, as well as fair, way to tackle disadvantage and prima face duty of justice to intervene: the possibility disease in the population. of reverting programed traits, when epigenetic informa- tion is a reliable biosensor, might efficiently prevent a Implications for Rawlsian Egalitarianism process of life-time accumulation of disadvantage that ends up in disease. The duty to develop and provide therapies and social This duty is only prima facie, meaning that on a tight policies to prevent the accumulation of epigenetic risk budget, resources may have to be diverted to meet more rests on the assumption that social justice requires cor- immediate priorities. But the importance for health recting the influence of causes of disadvantage for which justice of preventive measures should not be underesti- people are not responsible, natural and social alike. mated. True, health prevention competes for resources It might be objected that moderate egalitarians (e.g. with care for immediate health needs. But it can often be Rawls) are not committed to intervene in the distribu- both more efficient and just to prevent diseases, rather tion of the epigenetic predispositions people are born than cure them. In what follows, we shall present some with. It is only natural for the people favored by the considerations in support of the idea that acting on early natural (epi)genetic lottery to end up with better epigenetic determinants of diseases could be desirable health prospects. Those who are born with the worst from the point of view of efficiency. natural assets can at most expect society to design a Epigenetic disadvantage may matter in virtue of its tax system that redistributes wealth to their advantage. early onset. If one considers harm to a person in a life- They certainly cannot expect society to subsidize expen- course perspective, early disadvantage, even of milder sive medical services for the sake of correcting their quantity, may involve a large disutility in the long run. unequal life chances. This is clear in the ‘lifetime accumulation’ paradigm, in Against this objection, epigenetics forces us to recon- which genetic, epigenetic and socioeconomic determin- sider what counts as the natural/social boundary of ants of bad health reinforce each other, leading to a equality of opportunity. The paradigmatic social disad- continuous exposition to several drivers of diseases vantage, in Rawls, is class disadvantage, namely being and social exclusion. Any loss of realized ability due to born and growing, until maturity, in a family low in the adverse upbringing is considered to be a loss (in prod- hierarchy of income and power. Social disadvantage is uctivity force) and might even correlate with some social corrected by ensuring that all citizens, no matter their ‘bads’, such as socially expensive exclusion that society initial place in the social system, can access to education would necessarily have to tackle later on (Esping- and training that fits their natural predispositions. By Andersen, 2002; Heckman, 2008). contrast, the paradigmatic instance of natural disadvan- The idea of a crucial time window, in which early tage is the unequal distribution of genetic predispos- programing takes place, is a feature of social epigenetic itions, regarded as the outcome of a ‘natural lottery’. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 150 LOI ET AL. The metaphor of a ‘natural lottery’ is misleading in opportunity (e.g. everyone having access to the same the case of epigenetic traits that record environmental education or health care) is in theory compatible with impacts and are inter-generationally transmitted. outcome inequalities of any dimension. This assump- Consider an unfavorable predisposition to a common tion seems to be presupposed in the Rawlsian frame- disease that is (i) induced by childhood malnutrition works, where Fair Equality of Opportunity is distinct (‘Maternal diet and adult outset diseases predispos- from (and constrains) the Difference Principle, a prin- itions’ section) or maternal deprivation (‘Parenting ciple applying to the distribution of outcomes (income, style and psychological conditions’ section), (ii) highly wealth and the amount of power characteristic of every correlated with parental social disadvantage, (iii) trans- job and, more broadly, social position). The Difference mitted to the next generation. Grandchildren in a so- Principle permits all inequalities of income, wealth and cially disadvantaged family could inherit from their power that maximally benefit the worst off group in the socially disadvantaged parents and grandparents a population. Apparently, both Rawlsian equality of op- greater risk of metabolic disorders (‘Maternal diet and portunity and the Difference Principle are compatible adult outset diseases predispositions’ section), or stress with large socioeconomic inequalities: Fair Equality of responsitivity (‘Parenting style and psychological con- Opportunity allows all inequalities among the differ- ditions’ section). These are both ‘natural endowments’ ently talented and motivated, while the Difference and ‘socially generated’ endowments, partly explained Principle justifies unequal rewards for different jobs by social disadvantage produced by human institutions. (e.g. paying physicians and bank directors more than Even if a society where FEO is implemented subsidizes manual workers) when needed to attract more talented early health care and education, it may leave inherited and motivated people to perform the most difficult and epigenetic disadvantage untouched. challenging jobs, if this contributes to improving the On a restrictive interpretation of FEO, these inherited expectations of the least advantaged. Suppose that a differences are natural endowments because they are change in workplace hierarchies, e.g. an increase of dis- innate. Hence, FEO does not require financing medical ciplinary powers for managers, improves the annual treatments or social policies that can revert them or income of subordinate workers by 1000 E, while at prevent them from causing further disadvantage. But a the same time inducing in them a stress-related increase different, more extensive interpretation of FEO is at least in smoking behavior and the consumption of fatty food. equally plausible. The biological disadvantage of the Let us also imagine that this produces epigenetic grandchild is produced by adverse social conditions changes, which are passed to the next generation, so experienced by parents and grandparents. So it can be that at birth the children of subordinates are at greater described as an effect of the starting position in soci- risk of metabolic disease than the children of managers. ety, just as the paradigmatic form of opportunity in- In other words, there is a trade off between greater equality FEO is concerned with, namely unequal income expectations for generation N and more equal access to education. If required to promote equality of opportunities with respect to health for generation opportunity, a liberal state may legitimately attempt to N+ 1. In the Rawlsian theory, FEO constrains (being correct epigenetically inherited disadvantage by subsi- ‘lexically prior’ to) the application of the Difference dizing special interventions, just as it attempts to ‘level Principle. Thus, when these circumstances obtain, the the playing field’ by subsidizing the education of the lexical priority of the FEO represents an objection poor. against conferring more authority to managers to con- As pointed out in section ‘Reversible and preventable trol subordinates, otherwise permitted by the Difference epigenetic predispositions: correcting early disadvan- Principle. On the strict interpretation of FEO, this con- tage as investment’, this may take the form of designing straint is not justified: it does not affect the ‘expectations pharmacological or lifestyle correctives for reverting of those with the same abilities and aspirations’, but only programed phenotypes that are epigenetically measur- the expectations of people born with different natural able. But it is perhaps even more interesting to point out (epigenetic) endowments. On the broad interpretation, the consequences of the Rawlsian view, so interpreted, if FEO commits society to ensure that the expectations of epigenetic imprinting is not reversible. Paradoxically, individuals ‘should not be affected by their social class’, epigenetic inheritance could entail that equality of op- including when social class operates via natural endow- portunity can only be achieved by achieving a more ments, so it places limits to outcome inequalities in one equal distribution of outcomes. The ideal of equality of opportunity is usually put forward as an alternative generation for the sake of achieving more equal starting to the ideal of equality of outcome because equality of positions in the next. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 SOCIAL EPIGENETICS AND EQUALITY OF OPPORTUNITY 151 conception by parental donation of developmental Conclusions material: also environmental clues might program Our discussion of luck-egalitarian and Rawlsian equality adult traits (i.e. early in development or in utero) and of opportunity in light of epigenetic discoveries leads us their intergenerational similarities, i.e. if parents and their offspring share the developmental environment; to three broad conclusions that might be relevant to (iii) it suggests that biological inheritance is reversible public health: through environmental clues and thus influences by social structure. If we are to retain a distinction between (1) Epigenetics can be considered a biomarker of natural lottery and acquired traits we must explain how brute-luck disadvantage: Epigenetic screening it may fit this updated picture of social and biological might diagnose early-life and inherited insults due inheritance. Also, if we want to use that distinction in to factors beyond personal control, thus giving moral theory, we must explain why—if at all—the dis- people reasons to demand the provision of health tinction between biologically and socially determined services as a matter of equality of opportunity. traits retains its moral weight when transferred in the (2) Reversibility of programed phenotypes: The ad- new view suggested by DOHaD and epigenetics verse effects of inherited or early-life insults on findings. health measurable through the epigenome might While it is important to bear in mind the distinction be reversible through early pharmacological thera- between a Rawlsian and a luck-egalitarian approach, pies or environmental interventions, avoiding on the issue of correcting for (social) epigenetic disad- brute-luck health inequalities that are harder to vantage a significant convergence between the two tackle later on. approaches obtains. While the social circumstances (3) Nature vs. nurture: The social determination of experienced by our parents and grandparents have no epigenetic traits that can be inherited shows that direct influence on the distribution of genotypes (save innate traits are not necessarily insensitive to social from mating patterns, with which, however, a liberal structures. Reasons to tackle epigenetic disadvan- state cannot interfere), they may have a more direct in- tage, being an instance of inherited social disadvan- fluence on epigenetic predispositions. But if epigenetic tage, are also offered by the more restrictive traits are responsive to environmental cues, they can be Rawlsian version of equality of opportunity. influenced by social policy, and there is a fuzzy bound- ary between controversial ‘biopolitics’ (e.g. genetic en- More generally, it makes a significant difference hancement) and traditional social policy focused on the whether the natural inequalities mentioned by the main socioeconomic institutions (e.g. redistributive Rawlsian theory are identified with different genotypes taxation, access to education) in the Rawlsian tradition. or different epigenetic traits. Epigenetic channels of It is thus imperative from the point of view of public inheritance challenge the received view on the distinc- health and equality of opportunity to explore how the tion between social and biological inheritance of advan- different ways of conceptualizing this boundary affect tages and disadvantages. That view is based on what has direction of scientific enquiry, ethical views and policy been called the DNA-centric donation/conception theory development. of inheritance of features (Mameli, 2005): it explains bio- logical similarities between parents and their offspring through the donation at conception of a privileged de- Conflict of Interest velopmental material, DNA, while it leaves to cultural None declared. channels of transmission between parents and their offspring any other forms of similarity between them. The idea of the ‘natural lottery’ relies on that received Author Contributions view: traits that are explained by the donation of DNA at conception are due to the natural lottery, all the others All authors contributed equally to the design and con- are instead due to social structures. Epigenetics compli- ceptualisation of this article. Michele Loi and Lorenzo cates the picture in two ways: (i) it expands the list of del Savio wrote the sections ‘Introduction’ and ‘Health developmentally privileged material that can be passed Inequalities and Justice’. Lorenzo del Savio and Elia on at conception from parents to their offspring Stupka wrote ‘Epigenetics and Health Inequalities’. All (e.g. patterns of DNA-methylation); (ii) it suggests authors revised the whole manuscript and wrote the that biological inheritance does not happen only at section ‘Conclusion’. Downloaded from https://academic.oup.com/phe/article/6/2/142/1559493 by DeepDyve user on 13 July 2022 152 LOI ET AL. Champagne, F. (2008). Epigenetic Mechanisms and the Notes Transgenerational Effects of Maternal Care. Frontiers 1. Other influential theories start from an explicit ex- in Neuroendocrinology, 29, 386–397. Chmurzynska, A. (2010). 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The Ghost in Our Genes: Legal and Ethical Implications of Epigenetics. Health Matrix, 19, 1–43.

Journal

Public Health Ethics – Oxford University Press

Published: Jul 1, 2013

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