In the previous chapter we have reviewed how early life experiences could affect the epigenome and how this may in turn influence adult health. The epigenome could however be affected not only in early life but at different stages throughout the existence of an individual by factors such as food and exposure to chemicals or radiation.
Moreover, while most epigenetic changes were believed to be erased during gamete production in each new generation, in 2005 a report was published that challenged this belief and instead suggested that epigenetic alterations induced by such factors may persist in at least four subsequent generations.  Since then, other well documented examples of transgenerational effects with a presumed epigenetic basis have been reported.
It is as if our This memory is the epigenome.
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Hughes et al. have observed a correlation between food shortage and energy restriction during childhood and adolescence and the risk of developing colorectal cancer (CRC) later in life. They reported that individuals exposed to severe food shortage during the Dutch famine had less risk of developing CRC.  These findings suggest that apart from the prenatal and early postnatal phases (as discussed in the previous chapter), childhood and adolescence may also be periods of great epigenetic susceptibility.
Apart from a correlation between diet and disease in a single generation, studies have also demonstrated that there is a connection between the dietary intake in one generation and the life expectancy of another.  Researchers observed that shortage of food experienced by grandparents can affect the life expectancies of their same-gender grandchildren even though the latter never experience the scarcity themselves. Grandchildren of grandparents who experienced famine, were for instance less likely to die of cardiovascular disease while if food was plentiful, the incidence of diabetes mortality in the grandchildren was high.
This transgenerational effect depended upon the time in the grandparents' lives when food had been in short supply.Â For the grandfather it was in late childhood and just before puberty and for the grandmother it was when she was still in the womb. The researchers pointed out that these stages in life correlate with the development of sperm and ova respectively and therefore environmental information must have been imprinted on the gametes at the time of their formation. And indeed, various studies have shown that gametogenesis is a critical period in which epigenetic reprogramming occurs. 
Thus, even though in the previous chapter we have seen that maternal nutrition during pregnancy can affect the epigenome of the offspring, in reality one has to be thinking about his/her own diet and how this could affect future offspring long before planning a pregnancy! 
One possible explanation that has been suggested for the association between abundance of food and increased risk of cardiovascular disease and diabetes is that in times of food shortage the body modifies chemical processes going on in cells to increase the efficiency with which nutrients are absorbed and used for growth. If such a change persists throughout the life of an organism as well as across generations it could lead to excessive nutrient absorption in times when food is abundant. 
In other words, while providing a rapid way for the genome to respond and for organisms to adapt to a changing environment without having to change the base sequence of DNA, epigenetic mechanisms could increase the risk of disease if the individual encounters environmental conditions which are different from the supposed. 
These observations might provide one explanation as to why some people never gain weight irrespective of how much and what they eat. They could also explain the high incidence of childhood obesity and type II diabetes in some countries. Such conditions could be reflecting the lifestyles adopted by our ancestors in the past (e.g. in time of war). 
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And if the quantity of food we eat could have such a pronounced effect on the epigenome, what about the various artificial food additives that we consume daily? What effect could nutrient imbalances created by eating too much refined foods which lack some of the most important nutrients, or even food that has been genetically enhanced to have greater nutrient concentrations be having on the epigenome? Do we know what epigenetic effects medicines could have? Is the information provided to consumers with certain foods and medicinal products as reliable as claimed?
Thus, the observations presented in this section are significant not only because they suggest that epigenetic changes can be inherited by both children and grandchildren of exposed individuals and could therefore have a great impact on the way we view our responsibilities towards future generations, but also because they suggest that one day we might be able to prevent and cure certain disorders by ensuring a correct dietary intake. This however remains difficult to achieve because as the next sections will illustrate, the multitude of factors that can affect our epigenome make it very hard to actually identify the exact cause of disease.
4.1.2 Chemical exposure
Apart from food, or the lack of it, environmental chemicals can also induce epigenetic modifications. In some cases the effects of these modifications manifest themselves in the adult stage, even though the exposure would have occurred at an early stage in life.  There have also been reports that some of these effects are heritable and can thus affect future generations.
Anway and Skinner have highlighted the adverse effects that exposure of pregnant rats to endocrine disruptors  such as vinclozolin (used as a fungicide in the fruit industry) could have on male germ cell epigenome reprogramming, leading to transgenerational defects which result in low sperm counts, decreased sperm motility and infertility in up to four generations.  An association has also been found between low sperm counts and exposure to the pesticides alachlor, atrazine, metolachlor and diazinon. 
Male genital development has also been reported to be directly affected by exposure of pregnant rats to methoxychlor (used as an insecticide) and phthalates .  The mode of action of these chemicals involves a permanent alteration in the methylation patterns of sperm DNA.  Being permanent, the abnormal pathology is passed on to all progeny of subsequent generations even though these would never have been exposed to the harmful chemicals. The effect was not observed to diminish from one generation to the next.
Exposure to vinclozolin and methoxychlor has also been reported to induce breast tumors, prostate and kidney disease, immune diseases and premature aging in the first generation offspring. 
Even though in these studies rats were injected with extremely high doses of the toxins and thus such results might have no significance for humans, it is nonetheless worthwhile assessing whether exposure to these chemicals at the level actually present in the environment could actually affect human health.
Rat studies have also demonstrated that low-level exposures to bisphenol A during pregnancy and lactation periods can induce epigenetic alterations which could result in fertility impairments in the adult stage and may also increase cancer risk.  BisphenolÂ A (BPA) is a component of polycarbonate plastic which is used in the manufacturing of food and beverage containers, baby bottles and dental composite resins. A 2010 report from the U.S. FDA raised concerns regarding. 
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John Dalli, E.U. Commissioner for Health and Consumer Policy has stated that and for this reason E.U. states will ban the manufacture, import and sale of polycarbonate feeding bottles containing the compound as from mid-2011. 
Baccarelli and Bollati have reported that among the environmental chemicals which could induce aberrant changes in the epigenome one also finds metals such as nickel, cadmium, lead and arsenic.  Exposure to aluminum from personal care products has also been shown to modify genetic expression. 
Baccarelli and Bollati have also reported that methylmercury which may be present at elevated levels in seafood, benzene which is present in petrol fumes especially in the vicinity of petrol stations, as well as particulate matter  in urbanized areas can be agents of epigenetic alterations.  Hypermethylation of sperm DNA has for instance been observed in mice exposed to particulate matter. When pregnant mice were exposed, the germ cells within their embryos were effected. 
This evidence suggests that there might be a whole lot of environmental chemicals that could possibly trigger transgenerational affects and effect future generations by permanently altering the epigenome of the germ-line of an exposed individual. The question remains as to what extent can we extrapolate these observations to humans?
A study has revealed that most adults and children in the U.S. have accumulated numerous toxins in their body tissues, including pesticides and phthalates.  Other evidence has also confirmed that various common food products including baby food are contaminated with toxic chemicals such as dioxins.  Finally, in a toxicology study on umbilical cord blood, more than 200 synthetic chemicals were identified in the samples. These included fire retardants and pesticides.  In fact nowadays we know that many paediatric cancers and major congenital defects are directly related to toxic exposure during the prenatal period. 
Barrett quotes a December 2005 report of the CDC's National Survey on Family Growth as stating that Barett suggests that exposure to low-level contaminants present in the environment such as phthalates, dioxins and pesticides may be reducing our reproductive ability.
With the exception of some drugs and carcinogens, very little is known about how these synthetic chemicals to which we expose ourselves in the everyday environment of the home and workplace could actually affect our genes. 
This was the case with diethylstilboestrol (DES). DES was a pharmaceutical given to pregnant women between the 1940s and early 1970s to avoid miscarriage. Later on it was discovered that DES increased the risk of in the daughters and granddaughters of those to whom it was administered.  Effects on male offspring included increased risk of cryptorchidism (failure of the testes to descend in the scrotum during fetal development) and lower sperm counts.
Animal tests have proved that prenatal and neonatal exposure to DES causes a wide range of epigenetic changes in gene expression and that these epigenetic effects can be transmitted through the maternal germ-line and manifest themselves even after the exposure would have ceased. 
Besides maternal exposure, what the father is exposed to can also affect the epigenome.
Offspring of men exposed to solvents and other chemical agents in the workplace, including painters have been found to exhibit an increased risk of birth defects.  Fathers who are exposed to polycyclic aromatic hydrocarbons which are produced during the burning of fuels but also occur in grilled/barbecued meat and smoked fish,  also put their children at increased risks of developing brain tumors. 
It has also been reported that male mice exposed to cocaine had offspring which exhibited learning and memory difficulties even though the mothers were never given cocaine.  The same study also revealed that the resulting phenotype in the offspring was attributable to changes in the DNA methylation patters in sperm-producing tissues in the male parent.
All this evidence suggests that environmental pollutants and other synthetic chemicals or drugs may permanently alter the germ-line and epigenetic characteristics of all descendents of an individual exposed to toxins even if they themselves are never exposed to the same toxins.  This points out to the urgent need for screening and identifying those factors which have the potential to induce epigenetic modifications.
4.1.3 Smoking and drinking
If environmental toxins can have such profound effects as described in the previous section one may wonder what the effects of socially accepted habits such as smoking and drinking could be!
Alcohol consumption has been shown to affect gene function by removing methyl groups from genes.  Moreover, an association between colon cancer and consumption of alcohol has been reported to be particularly pronounced in individuals who are older than 60,  thus showing that gene expression can be influenced at all stages of life.
Once these genes are demethylated, the cancerous cells are activated to spread to other parts of the body.
Moreover, cigarette smoke can also influence the development and health of offspring in subsequent generations. For example a correlation has been found between the weight of 9-year-old children and the age at which their father started smoking. Fathers who started smoking when they were less than 11 years old had sons (but not daughters!) who were heavier than average compared to the sons of those who started smoking later in life or never smoked. 
Another study found that the grandchildren of women who smoked during their pregnancy had an increased risk of developing asthma early in life. 
People who smoke in their youth, have also been reported to sustain certain epigenetic changes, which may then increase the risk that their grandchildren reaching puberty early. 
In the past years, low-dose radiotherapy has increased survival rates of cancer patients considerably. However, there is risk that even cells which are not directly exposed to the ionizing radiation undergo epigenetic changes. This is known as the radiation-induced bystander effect  and scientists are well aware of the risk that ionizing radiation may affect methylation patterns and chromatin structure leading to epigenetic instability in the offspring of patients. 
Koturbash et al. even postulate that epigenetic changes induced by low-dose radiation may be responsible for the greater frequency of cancer across generations. 
4.1.5 The epigenome as a common heritage of mankind
In other words, This is also sustained in Article 1 of the UNESCO's Universal Declaration on the Human Genome and Human Rights which states that
The concept of a common heritage of mankind stems from the need not only to prevent that things of international importance become appropriated by a few individuals but also the need to preserve such things for future generations.  At the General Conference of 1997, the UNESCO has committed itself to safeguard the interests of future generations in the Declaration on the Responsibilities of the Present Generations Towards Future Generations. Thus the concept of intergenerational justice which requires us to consider the interests of future generations when making decisions and which is usually applied to environmental matters is also applicable to decisions regarding the integrity of our genome and epigenome. In other words, not only do future generations have a right to inherit a healthy planet but also a healthy genome.
Our increasing knowledge of epigenetic mechanisms has altered our understanding of disease causation. It has also highlighted the influential role played by our modern lifestyles and environment in shaping our epigenome and thus the expression of our genome. Nonetheless, many people, including highly educated individuals, are still unaware of the existence and mode of operation of epigenetic factors. Who has got the moral responsibility to effectively divulge such knowledge?
And once more people become aware that their actions will affect the health of their children and grandchildren for many years into the future would they have a moral obligation to live as a sort of guardians of their genome and epigenome to protect and conserve them for future generations?
This view of man as guardian of his epigenome is reflected in the Christian Stewardship Model of God in relation to creation and humankind. According to this model God has entrusted man with responsibility for conserving and preserving creation.  Joseph Cassidy and Edmund Pellegrino argue that according to this model, man is the steward over the human genome for future generations. 
What is uncertain is to what extent we should constrain our actions and lifestyles in order to protect future generations. Do we have a moral obligation to ensure that the food we eat or the air we breathe does not in any way jeopardize the integrity of our genome or epigenome? Wouldn't such a notion of responsibility towards future generations suffocate our individual autonomy and liberty? Do all individuals have a choice when it comes to deciding what to expose their epigenome to?
Should it be the consumers or the food producers or those individuals or companies who through their actions release noxious chemicals into the environment to shoulder the responsibility for conserving the epigenome? Could individuals or companies be held responsible for the development of illness in their children or grandchildren if the links between environmental exposure and disease that epigenetic research is revealing are ignored? For instance, daughters and granddaughters of women exposed to DES have filed lawsuits against its manufacturers. However, the granddaughter's claims have not been successful. and raise a number of new challenges and issues for the law courts.
Khan warns that unless the effort to reduce environmental hazards is a global one, it could be economically detrimental for those countries like the U.S. that take such initiative. In his paper he poses the following questions:
Should parents have a moral or even legal obligation to keep their children away from hazardous exposures?
Annas also quotes James Watson to have said that He questions whether unless we screen all neonates at birth for susceptibilities to cancer, all parents would have an obligation to keep children out of the sun, or whether a 'beach patrol' would be needed to check that parents apply the proper amount of suntan lotion to their child or, whether a genetic 'pass' would be needed to get to the beach.
Annas also mentions a case where two waiters were fired for trying to convince a pregnant woman not to drink alcohol on the basis that this might injure her fetus. This was in 1992 and at the time awareness on the effects of environmental exposures might have been limited. There was definitely no awareness of epigenetic mechanisms. But now that such awareness has increased, would the pregnant women have a moral obligation not to consume alcohol and the waiters to persuade her not to?
Will environmental events and exposures in past generations make employment or insurability more difficult for the current generation as new knowledge becomes available about how exposures in the past could influence the health of subsequent generations?
4.2 Environmental justice and access to health care
Epigenetic research highlights the effects of inequality in the living conditions of different individuals. In the previous section various examples have illustrated how exposure to toxic chemicals including pesticides and heavy metals, vehicle emissions and other airborne pollutants can affect the epigenome. Rothstein et al. sustain that many of these substances are not distributed randomly throughout society.  Poverty, low standards of living and poor working conditions increase the risk of exposure to such substances. Moreover, the same authors argue that the individuals who are mostly exposed to these factors would be more vulnerable to fall victim to such exposures because they would probably have other health conditions associated with their lifestyle, for which they would afford little if any medical treatment. In other words those that could be affected most are those with least access to health care.
What obligations does society have towards its most vulnerable members and those most likely to be affected by toxic exposures?
Rothstein argues that since epigenetic changes may be both preventable and reversible, But in reality, perhaps not even those countries with a universal health care system will be able to afford the latest epigenetic tests and therapies for all members of society. 
Finally, epigenetics is revealing that ensuring equitable access to food and healthcare resources will not provide an immediate solution to problems associated with poverty. Because epigenetic changes induced by our living and working conditions are heritable, it may take several generations to reverse the effects that poverty, discrimination and war could have on the individual. 
4.3 Intergenerational equity or eugenics?
In section 4.1.5 we have seen that intergenerational equity refers to the obligation of each generation to serve as a guardian of the genome and epigenome to safeguard it from harm caused by exposure to environmental hazards. But is our moral duty limited to pass on the genome and epigenome in the same state that we received it or do we have a responsibility to pass it on in an improved state?
In contrast to the Stewardship Model of creation mentioned previously, another model, the Created Co-creator Model, while recognizing that only God can create ex nihilo it sustains that the Creator has endowed us with the ability (and responsibility) to create and bring to completion this 'project' of creation. Nonetheless, our ability to create is limited to transforming living organisms to make them 'more complete'.  In other words, because we are co-creators, we have greater freedom than in the Stewardship Model to intervene into our genetic material.
Jirtle argues that people inherit their genome  Jean-Pierre Issa believes that
Then again, while sustaining that our duty to preserve the genome and epigenome for future generations is something everybody would agree upon, Rothstein fears that our desire to pass on the epigenome in an improved state might lead to eugenics.
Finally, Lammers and Peters point out that by trying to alter our genetic constitution we may endanger the entire human species. Evolution has partially depended on random changes in the genetic material and the selection of those organisms with the fittest combination of genes.  Would we be threatening the process of evolution if we try to improve our epigenome?
On the other hand, perhaps by learning to fix epigenetic defects we may intervene just in time to keep the human species from being wiped out by a tide of environmentally-induced diseases. To manipulate or not to manipulate our epigenome could thus, in either case, prove to be dangerous for the future of humanity.
4.4 Concluding remarks
In the past few years, several studies have analaysed the relation between exposure to environmental chemicals and changes in the epigenome. Several chemicals that induce epigenetic changes have been identified, including heavy metals, pesticides and other endocrine disruptors, vehicle exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, radioactivity and even excessive nutrients.
However, it is not easy to establish a clear-cut relationship between environmental factors, epigenetic changes and the various diseases that are suspected to be caused by epigenetic mechanisms (including cancers as well as respiratory, cardiovascular, reproductive, autoimmune, and neurobehavioral disorders). This is mainly because epigenetic changes might not manifest themselves immediately and at times not even in the exposed generation. However, the problem is also compounded by the fact that human studies are often based on easily obtainable tissues such as blood, while epigenetic patters tend to be tissue-specific. Thus the results of such studies may not necessarily reflect the effect on other tissue types.
Epigenetic research has also revealed that past and future generations may be linked in ways we never imagined. Our lives, the air we breathe, what we eat and drink, the medicines we take, the things we do and experience, can work their way into the germ-line and resonate down the ages by affecting our children and grandchildren in yet unimaginable ways, despite the fact that they never experience these things themselves.
Thus studying epigenetic changes and the environmental factors that induce them could prove to be very important not only for developing treatments for individuals suffering from epigenetic disorders. If we assume moral responsibility for our actions and take the necessary actions to regulate or avoid exposure to such factors we could prevent that our lifestyles have a negative impact on future generations.