22 May 2014 — Links International Journal of Socialist Renewal
The central problem of our age has therefore become the contamination of man’s total environment with such substances of incredible potential for harm—substances that accumulate in the tissue of plants and animals and even penetrate the germ cells to shatter or alter the very material of heredity upon which the shape of the future depends. — Rachel Carson, Silent Spring, 1962
There is an epidemic of diseases now sweeping the industrialised countries. These include obesity, diabetes type 2, high infertility rates affecting both men and women, high blood pressure, thyroid and central nervous system as well as cancers, mainly breast and prostate cancers. In addition to all of this, immune deficiencies.
The figure for just diabetes alone gives an indication of the problem. There are 170 million people worldwide suffering from diabetes and it is expected to rise to 336 million by 2030. The toll on the public health system is enormous, not to mention the grief suffered by these families. As if that was not enough, there is also evidence that younger and younger children are suffering from diseases that a decade ago only affected adults.
Another terrible problem is the increasing rates of mental illnesses affecting our children, attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD), including Asperger’s; rates of schizophrenia are increasing.
The number of children diagnosed with ADHD increased by 33% from 1997 to 2008 and by more than 21% between 2003 and 2007, among all socioeconomic groups. Autism increased by 289.5% from 1997 to 2008 in one study group and by 57% in 10 different areas of the US from 2002 to 2006. Diagnosed autism was more prevalent among boys but increased in all major sex, racial and ethnic categories (Latham et al., 2012).
Obesity affects over 33% of North Americans. No US state has an obesity rate of less than 20%. The increase is particularly alarming among children; obesity in children aged 6-18 years rose from 6% to 15% between 1980 and 2000 in the US. Obesity has increased among men, children, citizens over 65 years and the black population.
Some 14 million Australians are overweight or obese. Obesity has overtaken smoking as the leading cause of premature death and illness in Australia. Indigenous people are the 4th most likely population in the world to suffer from diabetes type 2. It is not obesity per se that is a problem but obesity contributes to the development of multiple adverse health effects, including heart disease and up to 15% of all cancers, including brain cancer.
This wave of ill health has generally been ascribed to terrible diets, high sugar content, high cholesterol intake, too much fat and trans fats (some artificial unsaturated fats). It is probable that bad diets and bad genes, to a certain extent, make a contribution but there is another explanation that biochemists are just discovering — the effects of epigenetic transgenerational inheritance. Epigenetics means the study of heritable changes in gene expression, occurring without changes in DNA sequence (Wynter et al., 2007). Epigenetics comes from a Greek word meaning overlaid “on top of genetics”. “Epigenetic transgenerational inheritance” refers to the transmission of a biological trait to subsequent generations via epigenetic modifications in the germline.
The deleterious effects of chemicals are transmitted in the germline, through epigenetics, which makes the change permanent in all succeeding generations.
It is due to minute traces of industrially synthesised, complex chemicals in food and water. Nature has never before been exposed to these human-made industrial chemicals and so there is no pathway for their elimination from the environment by bacteria or any other method.
Rachel Carson, in her book Silent Spring, written in 1962, which was vigorously attacked by the chemical companies at the time, warned of the real dangers of these problems, even though the biological mechanisms were then unknown.
There are more than 13 million deaths every year due to environmental pollutants. Some 24% of diseases are estimated to be caused by environmental exposures that could be averted. In the US, 148 different environmental chemicals were found in the blood and urine of the population, an indication of the extent of exposure to environmental chemicals (Hou et al., 2012). It has been known for some time that many chemicals, even in minute amounts, can have a deleterious effect on our health if eaten or present in the water supply. This was easy to prove by experiments on rats and mice and unfortunate accidents in which industrial workers were exposed to high concentrations of toxic doses.
However, it was also thought if we avoided contaminants in our food and water, our children and grandchildren would not be affected. It is now known that there could be a permanent effect on grandchildren and great grandchildren who have never been exposed to these chemicals.
Human exposure is an unavoidable everyday occurrence not limited to occupational sources. These chemicals are concentrated in the food chain, mainly through meat and fish and in the water we drink and even through our skin by handling such things as thermal receipts from supermarkets. These chemicals are found in the serum of the general population, in maternal serum and cord blood, and contribute to adverse health effects among babies, children, adults and animals.
Probably the only way, one can minimise exposure to these chemicals is to switch to a vegan diet.
Concerns related to these compounds cannot be dismissed as merely “alarmist”, but reflect the growing awareness of their serious impact on public health. The new discovery of epigenetic transgenerational inheritance has only come about in the last three years. It was partly dependent on the sequencing of the 3 billion bases in the human DNA, known as the Human Genome Project, which was finished in 2001. In the last few years our understanding of how the DNA sequence is read, and the mechanisms of control of the access to that translation, has increased enormously.
DNA is the blueprint for each human being and is different for each individual. DNA consists of four nucleotides in a long chain: adenine, guanine, thymine and cytosine, referred to as AGTC. Every cell in the body contains the same DNA in the cell nucleus as every other cell, in the form of two lots of 22 chromosomes, one from the mother and another set from the father, as well as two X chromosomes if female and an X and Y chromosome if male, giving a total of 46 chromosomes. However in the gonads, the ovary and the sperm cells contain only half the DNA: 23 chromosomes.
It was a shock for many geneticists to discover that there are only 30,000-40,000 genes that are translated into proteins in humans, far fewer than the expected 100,000 protein-coding genes, and only twice as many genes as in a fruit fly. The genes coding for translated proteins make up only 1.5% of the genome, the rest of the DNA — once dismissed as junk DNA — controls the mechanism to determine when and how the genes are switched on, providing the organisational tools to develop and build tissue and organs in an ordered fashion.
In the cell nucleus the DNA is wrapped around a core of proteins, 8 histones, very much like a piece of string wrapped around a tennis ball. The most well-studied mechanism of epigenetics is methylation, a chemical change brought about by cellular enzymes. There are two ways in which this operates, a methylation of the DNA, specifically, a cytosine nucleotide to form 5 methyl cytosine and methylation of the proteins, the histones to shut down access to the genes, so that they cannot be transcribed into proteins. If the methylation pattern is not right, the genes can be switched off, a process called gene silencing. Sometimes certain genes will be switched on in error, leading to a cancer. Histones can also be chemically modified by other side chains besides methylation, such as acetylation, phosphorylation and very large side chains such as ubiquitination, sumoylation and ADP ribosylation.
The main thing to note is that access to the DNA is a very dynamic, complex process, controlled by an army of enzymes and proteins carrying out a multitude of chemical modifications of the histones and the DNA. Non-coding RNA also known as microRNA, only discovered in 1996 in plants with Craig and Mello winning the 2006 Nobel Prize for Medicine, should also be mentioned, as non-coding RNA also plays a key role in this process. Both excessive methylation and under-methylated DNA can result from exposure to industrial chemicals. For some genes, even a small change in the level of DNA methylation at a few cytosine and guanosine sites might subtly alter gene expression and increase the risk of disease.
It is through epigenetics that humans react to the environment and how the environment influences growth, development and health of humans. This is how we have changed over 2 million years to adapt to a changing environment, such as ice ages, temperature changes, skin colour and digestion of different foods, as the plants evolved. This is why some Europeans are sensitive to peanuts, as they haven’t been around as long as Africans to adapt their immune system to peanuts. It is now realised that these epigenetic adaptations can be permanent and passed onto the 4th generation and beyond (Figure1).
Figure 1: If the pregnant mother is exposed to a toxic chemical, then it is possible that three generations are exposed, F0, F1 and F2. Epigenetic transgenerational inheritance occurs when the great granddaughter or the fourth (F4) generation who has had no exposure exhibits similar symptoms.
Methylation is essential for genetic stability of the genome. The methylation of DNA is involved in a number of different processes essential to the cell’s normal functioning: i) parental imprinting, where one gene from the mother or the father is shut down to allow a single, normal dose; ii) random inactivation of the second X chromosome in all cells in females; iii) control of unruly DNA elements, which can jump along chromosomes and cause a long list of diseases. Further complications are that during fetal development, the DNA of the newly fertilised egg is alternatively demethylated and remethylated to allow for sex differences. The complex factors that control methylation and essentially protect some regions of the genome and allow other regions to be demethylated and then remethylated are still totally unknown.
Thus any disruption of this DNA methylation or epigenome can spell disaster for the offspring. Any interference in this process usually produces a deformed individual or if a healthy baby is born, later on in life he/she may succumb to an early death. This complexity of DNA methylation accounts for the fact that it has been extremely difficult to clone any animal and not have it die early of a disease. However, there is now a clear mechanism as to how these particular industrial chemicals can cause permanent damage to human health.
World War II had a permanent effect on individuals and their offspring, who were exposed to the famine during the Dutch Hunger Winter in 1944-45. It was found that the children who were conceived by these women during the famine, and who were examined some 60 years on, had much less DNA methylation of one of the important genes that control growth and development, compared to their unexposed brothers or sisters. Other diseases, associated with exposure of the mother to famine, include schizophrenia and coronary heart disease (Heijmans et al., 2008).
One of the first known examples of how exposure in utero to a pharmaceutical could have permanent effects on the fetus was the use of diethylstilbesterol (DES). DES is classified as an endocrine disruptor. From the 1940s until the 1980s, DES was given to pregnant women in the mistaken belief it would reduce complications from pregnancy and miscarriages. DES was aggressively marketed and routinely prescribed, saying it was safe for pregnant women and the developing baby, with sales peaking in 1953. In 1971 it was discovered that a rare vaginal tumour, clear cell adenocarcinoma, developed in girls and women who had been exposed to this drug in utero. Despite proof from clinical trials in the 1950s that the use of DES showed no benefit during pregnancy, DES continued to be given to pregnant women throughout the 1960s.
Further, DES was prescribed to pre-pubescent girls to bring on puberty and to those women who were considered to be too tall, to stop them growing, despite the fact DES was clearly linked to cancers. The number of women exposed to DES from 1940-1971 is unknown but could be as high as 2 million in the USA, although it was also prescribed in France, Netherlands and Britain.
Worse was to come with a study showing that DES was effective as a contraceptive after intercourse and was handed out at many university health services and especially in emergency situations such as rape or incest. It wasn’t until 1978 that DES was removed by the US Food and Drug Administration for use in suppressing lactation and to prevent breast engorgement after giving birth. Only in 1997 did the last manufacturer of DES, Eli-Lilly, stop marketing the drug.
This epigenetic carcinogen induced infertility and cancers in the daughters and granddaughters, if the mother had been injected with DES (Newbold, 2004). DES has been shown to alter gene methylation patterns in mice. Initially, fewer studies documented risks of pre-natal exposure to diethylstilbestrol on males (referred to as “DES sons”). In the 1970s and early 1980s, studies published on pre-natally DES-exposed males investigated increased risk of testicular cancer, infertility and urogenital abnormalities in development, such as hypospadias, a nasty birth defect of the urethra where the opening of the male orifice opens along the underside of the shaft instead of the tip of the penis.
Bisphenol A (BPA) is considered another source of epigenetic transgenerational inheritance. In commercial use since 1957, BPA is used in the production of plastics and resins that are used in food and drink containers, flame retardants, dental sealants and dental fillings, thermal paper used in shopping receipts, sports equipment, CDs and DVDs and lining water pipes for industrial purposes. The plastic is clear and tough and was used in a variety of common consumer goods but the most dangerous was its use in baby bottles as well as bottles selling water.
The European Union, Canada and the US have banned BPA use in baby bottles. A 2010 report from the United States Food and Drug Administration warned of possible hazards to fetuses, infants, and young children. A recent epidemiological study has linked prenatal exposure to BPA with subtle, gender-specific alterations in behaviour of two-year olds. BPA exposure is associated with prostate and breast cancer, reproductive system effects, sterility, miscarriage, obesity, effects on changes in cell divisions in the oocyte, changes in fetal development and the development of polycystic in the adult ovary. Almost all exposure, including that of children, has been thought to occur through diet.
Many of these chemicals are classed as endocrine disruptors, capable of changing normal brain development. Laboratory studies exposing experimental animals to BPA during the pre-natal and neonatal periods have reported neurodevelopmental and behavioural effects including depression-like symptoms and memory. Hyperactivity in male mice has also been demonstrated in response to perinatal exposure to BPA. If this toxin behaved in the same way in humans, it would be responsible for ADHD. Others have shown that exposure affects neurotransmitter levels and gene expression patterns in the brain (Perera & Herbstman, 2008). Experimental evidence indicates that exposure to environmentally relevant doses of BPA during pregnancy abrogates sexual dimorphism in brain structure and behaviour and disrupts cognition, social behaviour and other aspects of brain function.
In 2010, Canada became the first country to declare BPA a toxic substance. Plastic bottles left in the sun, in a car or heated in the microwave can have small amounts of BPA leached out into the water. Epoxy resins containing BPA are used as coatings on the inside of many food and drink cans. Cans containing food were lined with a plastic coating to stop the leaching of the metals used in soldering the can together but in this case the solution is worse than the original problem. Some 95% of 2500 people tested in 2003 in the US had BPA in their urine samples. When buying plastic containers, everyone should check that it contains no BPA. Food Standards Australia and New Zealand do not consider BPA a health risk (http://www.productsafety.gov.au/content/index.phtml/itemId/971446.)
Phthalates are a group of diesters of phthalic acid used as plasticisers to soften and increase the flexibility of Poly Vinyl Chloride (PVC) plastics. Human exposure to phthalates mainly occurs through foods, because of our habit in wrapping food with cling wrap to put in the fridge so it doesn’t get wet. Because phthalate plasticisers are not chemically bound to PVC, they can easily leach and evaporate into food or the atmosphere. When ingested through food contamination, diethylhexyl phthalate (DEHP) is converted by intestinal lipases to mono-(2-ethylhexyl) phthalate (MEHP), which is then preferentially absorbed. Dibutyl phthalate (DBP) is used as a component of latex adhesives and glues. It is also used in cosmetics and other personal care products, as a plasticiser in cellulose plastics, and as a solvent for dyes. They are also found in building materials, medical devices, detergents, packaging, children’s toys, pharmaceuticals, food products and textiles.
Phthalates are also associated with a number of adverse reproductive and developmental effects including undescended testes and adverse neonatal neurodevelopment among girls. Phthalate exposure has also been associated with elevated baby fat (BMI) during the first three years of life. High maternal serum and cord blood concentrations of DEHP are related to the incidence of attention deficit disorder and other childhood conditions. DEHP is an anti-androgen as it prevents androgens such as testosterone from binding to the cell receptor. It can also lead to reproductive effects such as the breakdown of ovarian follicles in the ovulating woman. Each woman is born with millions of follicles but will only ovulate about 400 times in a lifetime. This effect could explain why women in their 30s are finding it difficult to conceive. DEHP can also inhibit follicle-stimulating hormone activity, pre eclampsia, (high blood pressure which can cause seizures in a pregnant woman), miscarriage, reduced levels of oestrogen, prolonged estrus and premature breast development. Phthalates also can alter placental function and development. No wonder that female infertility is increasing and male sperm count is decreasing worldwide (Perera & Herbstman, 2008).
Dioxin and autism
The health effects of exposure of humans to dioxin, 2,3,7 8 tetrachlorodibenzo–p-dioxin, or TCDD, the active agent in Agent Orange, which was used extensively in the Vietnam War, have been well documented (see earlier article in links.org.au/node/3636).
The developmental effects on the fetus if the mother has been exposed to dioxin through the food chain or water supplies may be much more important than the effects in adults. Dioxin promotes teratogenicity or birth defects, and congenital defects in the off-spring, including such problems as cleft lip, cleft palate, club foot, hydrocephalus, neural tube defects, fused fingers, muscle malformations and paralysis, kidney damage, spina bifida and some developmental disabilities. These include disturbances of tooth development and of sexual development.
Other effects on the developing fetus include impairment of the immune system, liver damage, heart problems, wasting disease, skeletal deformities, changes in endocrine homeostasis (the endocrine glands release hormones in responses to stress and injury), and disrupted growth and development, absorption of nutrients, energy metabolism, water and electrolyte balance, reproduction, birth and lactation, reduction in steroid-dependent response, modification of cell growth, growth of tissues and differentiation of tissues.
An Australian study found some evidence of increased heart defects and Down’s syndrome in babies born to mothers exposed to dioxin.
Another factor that is very concerning is the possibility that dioxin contamination of the human diet could be a contributory factor in the development of autism in children. The etiology of autism has been difficult to determine. Autism is multifactorial, some with a genetic basis, either a familial or a spontaneous mutation, but others are environmental. Autism Spectrum Disorders (ASD) result from a complex combination of genetic, epigenetic, environmental toxins, air pollution, organophosphates, pesticides and heavy metals. There has been a dramatic increase in ASD since the 1980s. To a certain extent, this is due to both a greater awareness of the disorder but there are likely additional factors contributing to the increase, including environmental factors. The prevalence of ASDs is currently two in 100 children in the United States, with numbers increasing each year (Centers for Disease Control and Prevention, 2012).There is a difference in sex ratios of sufferers of autism where it is four times more common in boys than girls.
The mechanism of this environmental disaster is that dioxin acts to transform the epigenome. This is well documented in animal studies (Mannikam et al., 2012 & 2013). Chronic kidney disease in humans is correlated with high dioxin levels (Couture et al., 1990). Similar to kidney disease, ovary disease also appears to be the outcome of epigenetic transgenerational inheritance. The finding that dioxin promotes epigenetic transgenerational inheritance of disease is devastating to those populations directly affected, which includes the entire peoples of Vietnam, Laos and Cambodia, and all Vietnam veterans from 1961 to 1973. The dioxin-modified sperm epigenome appears to be permanently reprogrammed similar to an imprinted gene. The changed sperm epigenome is protected from DNA demethylation and reprogramming after fertilisation and in the following generations, as described above. That is why the children of Vietnam veterans in the US and Australia, who fought in the war, are affected, despite the fact the mother would not have been exposed to large doses of dioxin.
A new term has recently been coined, namely Obesogens. They are chemical compounds that disrupt normal development and balance of lipid metabolism, which in some cases can lead to obesity. Obesogens may be functionally defined as chemicals that inappropriately alter lipid homeostasis and fat storage, change metabolic set points, disrupt energy balance or modify the regulation of appetite and the feeling of being full to promote fat accumulation and obesity. One of these class of chemicals is a group of compounds that combine the mineral tin with chemical side chains, such as tributyltin. Organotin compounds may contribute to the escalating problem of obesity. Organotins affect other endocrine tissues such as pituitary, gonads and thyroid, and large doses can affect the bone, central nervous system and gastrointestinal tract. Organotins are immunotoxic and they lead to implantation failure of the fetus and fetal death, along with uterine and placenta defects. Children may have intakes of organotins up to eight times higher than adults.
Until now, 20 chemicals have been found responsible for making one obese (Latham et al.. 2012). There is some overlap as other chemicals discussed above can also be called obesogens: the phthalates, DES and BPA. However the mechanism of the obesogens is the same, permanent changes in the epigenome of the germ cells, affecting reproduction and health of all future generations.
Approximately, 800 distinct chemicals have been classified as endocrine disruptors. Endocrine disruptors are chemicals that affect endocrine glands, their function, hormonal levels, receptors and signaling pathways. Some endocrine disruptors have been found mostly to act on the epigenome. New studies will be needed to determine which of these 800 chemicals are also permanently changing the epigenome of future generations. Another new term has arisen, epigenopathies, meaning pathologies resulting from disturbances in the epigenetics of the genome. One of these is possibly the Autism Spectrum Disorders. A number of rare brain disorders have also pointed to the disruption of chromatin remodeling and DNA methylation patterns in the developing brain. Currently, the world’s female population is facing an increasing incidence of primary ovarian insufficiency, characterised by a loss of follicle reserves in the ovary and an increasing incidence of polycystic ovarian disease. All these health problems could be due to these industrial chemicals still in the environment, being absorbed and then stored in fat tissue in humans,(Hart et al. 2004, Vujovic, 2009). Obesity may be another of these epigenopathies.
In the sperm of the DNA of rats treated with low concentrations of dioxin that only affected the F4 generation, it was found there were 50 DNA Methylation Regions altered, affecting every aspect of normal cell function (Mannikam et al. 2012). In the Comparative Toxicogenomics Database, BPA was found to produce 1232 changes in methylation pattern of unique genes. The 5 most frequently used phthalates (DEHP/MEHP and DBP/BBP/MBP) were found to have 265 interactions with unique genes/proteins, respectively (Singh et al., 2012). Exposed to a combination of chemicals, we don’t know how many changes are already present in our genome. It is calculated that it would take 10 generations to restore the damage to 1250 methylation sites, to revert to an epigenome, if one partner was totally unaffected by industrial chemicals. A normal generation in humans is 30 years. This would mean at least another 300 years would have to pass after ending this chemical assault on our bodies, before humans would once again enjoy full health.
For the first time in the history of life on Earth, we are subjected to poisonous and toxic chemicals from the moment of conception to the day of death. These chemicals that change the basis of our genetic inheritance are everywhere, in every corner of the Earth, even the most remote areas of the Amazon jungles, the Sahara, Iceland and Antarctica. These chemicals, industrially synthesised and never before found in nature, are present in our water. Their presence is not even tested in our water supply, let alone the authorities attempting to purify our drinking water. Most of them are so stable that they are not broken down by bacteria and normal processes in the soil.
The chemicals are present in tiny amounts but are horrendously potent. They are affecting and will affect all life on Earth.
We are faced with a massive problem and it is essential that we change the method of production in a huge number of areas, not only of many industrial chemicals but production of plastics and many other processes that so far have not been investigated.
We must end the treatment of the environment and the entire Earth as if it was just a big mine to be exploited. We must finish with the era of cheap and nasty plastic items, on sale in every area for domestic use and then thrown away. It entails a 180-degree turn in manufacturing and economics and a rethink of how this can be carried out safely and sustainably, with no damage to the environment.
It will require a revolution of people’s power, a direct assault on capitalism to put a final end to the pollution from the chemical industry and to remove these toxins from our environment and to finally enjoy a full life in full health.
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