Archives for category: Epigenetics

From Harvard Gazette:

Life evolved in a toxic world long before humans began polluting it, according to a University of Massachusettsenvironmental toxicologist, who added that understanding life’s evolutionary response to environmental poisons can help people to fight destructive effects.

Emily Monosson, an adjunct professor in the UMass Department of Environmental Conservation and author of the book “Evolution in a Toxic World,” said that an understanding of both how rapidly and how slowly life can evolve to fight toxic pollutants is largely missing from toxicology, which is the science of understanding the effects of poisons on life, particularly human life.

Monosson, who spoke Thursday at Harvard’s Haller Hall in an event sponsored by the Harvard Museum of Natural History, said lessons from our evolutionary past that might help us avoid trouble have been ignored by toxicologists and industry alike.

Monosson said she wrote the book in an effort to get toxicologists to think differently about their field, which she said still uses tools that are 40 years old and badly need updating.

“The basic point of doing this book is to get toxicologists to look differently at our field,” Monosson said. “Toxicology needs to change.”

Examples abound on the ramifications of rapid evolution, she said. Bacteria reproduce so fast that they quickly evolve resistance to drugs used to treat disease, resulting in frightening new ailments such as multidrug-resistant tuberculosis. Similarly, insects can rapidly evolve resistance to pesticides, and weeds can evolve resistance to herbicides.

“Roundup Ready” soybeans offer an example where a better understanding of the rapidity of evolution might have helped, Monosson said. The soybean was genetically modified to be resistant to the herbicide Roundup, which could then be sprayed on soybean fields, where it would kill weeds but not the soybeans. Officials believed that the weeds would not become resistant to Roundup. But after blanket applications, it appears that some resistance is evolving.

Slow evolutionary change also holds lessons for toxicologists and industry, Monosson said. Estrogen receptors help to control the body’s use of the critical reproductive hormone. Some industrial chemicals bond with the receptor, widely disrupting reproduction of an array of creatures.

Estrogen receptors are highly conserved, meaning they are widespread among many kinds of creatures and have changed extremely slowly over time, an indication of their evolutionary importance. An understanding of that importance would have helped officials predict that chemicals interfering with them would have widespread and deleterious environmental effects, Monosson said.

“There’s a lot of problems we could have avoided if we understood the power of evolution in the presence of toxic chemicals,” Monosson said.

It is unknown how humans today will respond to the many chemicals, usually at low levels, that our bodies are carrying. Some of these chemicals may be harmless alone but could have interactions with other chemicals in our bodies, Monosson said.

“Those chemicals in us today weren’t in our grandparents,” Monosson said. “If we take an evolutionary approach to understand how systems evolved to detoxify chemicals, maybe we can learn how to do it [ourselves].”

A toxic Earth is nothing new to life, Monosson said. When life began 3.8 billion years ago, there were poisons all around. Besides the presence of metals and other toxins in the environment, early microbes were bombarded from above. The early Earth had little oxygen in the atmosphere and no protective ozone layer to shield the microbes from ultraviolet (UV) rays.

In response, early life evolved an enzyme, photolyase, to repair the UV damage to DNA. That enzyme, though lost in most mammals, remains widespread in other types of creatures.

Another early example involved oxygen, which is very reactive and on the early Earth acted like a poison. Life has since evolved to handle and depend on oxygen. One strategy evolved to break down hydrogen peroxide, a highly toxic chemical that forms naturally in the presence of oxygen, water, and UV rays. Early life developed an enzyme called catalase to detoxify hydrogen peroxide, accelerating the natural breakdown process from weeks to a fraction of a second.

In the future, climate change promises to alter the range of many creatures, putting them in new environments to which they’ll have to adapt. The ozone hole is exposing creatures to higher levels of UV radiation than they’re adapted to handle. And human-generated pollutants continue to be released into the environment, presenting an environmental challenge for a wide array of creatures.

Some, like Hudson River fish that have evolved to thrive despite the presence of polychlorinated biphenyls (PCBs), will evolve their own solutions, but others may need human intervention to handle an environment whose toxicity is changing much more rapidly than in the past.

“The problem today is that in a blink of time, we changed the Earth,” Monosson said. “We’ve added a lot of new synthetic chemicals and redistributed a lot of natural chemicals.”

Read entire article here.

Image by Kris Snibbe/Harvard Staff Photographer.

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Lindsey Konkel has just published an outstanding article on Environmental Health News.  Here is an excerpt:

When doctors told Wanda Ford her 2-year-old son had lead poisoning, she never suspected that the back yard in her low-income neighborhood was the likely culprit.

Ford knew that exposure to the heavy metal could be dangerous. So when she and her husband moved into the Lower Lincoln Street neighborhood, Ford, then pregnant, took steps to make sure their 100-year-old home was lead-free.

“We never thought to test the soil – my son played in the back yard all the time,” said Ford, whose son is now seven.

It’s long been known that children in poorer neighborhoods like Ford’s are more likely to be exposed to lead, industrial emissions, vehicle exhaust and other contaminants. Now, scientists are beginning to suspect that low-income children aren’t just more exposed – they actually may be more biologically susceptible to them, even at low levels.

A growing body of research suggests that the chronic stressors of poverty may fundamentally alter the way the body reacts to pollutants, especially in young children. Several studies have found that such stress may exacerbate the effects of lead on children’s developing brains, while others reported more asthma symptoms in kids with simultaneous exposure to air pollution and socioeconomic problems.

Everyone experiences stress occasionally; it can improve focus and performance to overcome obstacles at work, during athletic competitions, or in everyday life. But stress also can harm the body.

“When the stress is chronic and the stressors are out of our control, we experience it as a threat rather than a challenge,” said Dr. Rosalind Wright, a physician and epidemiologist at the Harvard School of Public Health. “This type of stress can have negative, lasting effects on key systems in the body. It’s like having the fight or flight response turned on all the time.”

Schools and homes next to refineries and Superfund sites, farm workers drinking toxic water, urban children breathing exhaust from congested streets. Many of these people are living in poverty or with low incomes, and they have to cope with socioeconomic problems as well as high exposure to pollutants. Scientists say living in such areas and facing financial strain, racial issues and high crime rates can wear down the systems responsible for controlling immunity and hormones. Hormones needed for proper brain development may be altered, or the immune system may continually release inflammatory molecules into the blood.

“This may make you more susceptible to everything else around you, including pollution,” said Jane Clougherty, an exposure scientist and epidemiologist at the University of Pittsburgh Graduate School of Public Health.

One + one = four

Stress, when combined with certain pollutants, may produce a much greater health effect than either stress or pollution alone.

“It would be like adding one and one together and getting three or four,” said Dr. Ted Schettler, science director of the Science and Environmental Health Network, a non-profit organization focused on applying science to promote health. “Socioeconomic status may affect underlying biology, making exposure to certain chemicals more adverse for the poorer kid.”

In Worcester, about 40 miles west of Boston, nearly one in five residents lives below poverty level, almost double the Massachusetts average, according to 2010 U.S. Census data. Its median household income is roughly 30 percent lower than the state’s.

Worcester is representative of many old manufacturing towns across the country. “With a decline in manufacturing, you get a decline in certain types of pollution, but you are also left with ongoing problems such as lead contamination in soil, which is typical of a lot of older American towns and cities,” said Katherine Kiel, an environmental economist at the College of the Holy Cross in Worcester. “Low-income housing is often built where property is cheapest. Unfortunately, these areas often have more pollution.”

Socioeconomic stress “may make you more susceptible to everything else around you, including pollution.  Jane Clougherty, University of PittsburghThe eaves of Ford’s home – one of Worcester’s iconic triple-decker apartment houses – are blackened by soot from trucks and cars. From her front porch, she can see the on-ramp to the interstate highway that bisects the city.

“This feels like a depressed town. There are a lot of neglected, dilapidated places. It’s not very child-friendly,” said Ford, who is not using her real name for fear that her son will be bullied at school about his learning disabilities.

Ford is black, as is roughly 12 percent of Worcester. One small study published last year found that women in Boston who faced racial discrimination and community violence had higher levels of a stress hormone linked to preterm births.

Gang activity and a drug raid at a house nearby have brought community violence close to home. “My husband and I didn’t see it at first when we moved here, but it’s pervasive,” said Ford.

Rates of violent crimes in Worcester are about 17 percent higher than the national average. In 2010, there were roughly 471 assaults, armed robberies and murders per 100,000 inhabitants in Worcester. The national average for that same period was 404 violent crimes per 100,000 people, according to the FBI’s Uniform Crime Reports.

She worries constantly about the safety of her kids. Four of them, all under the age of 15, live at home.

When her son was born in 2004, he seemed healthy. “Looking back, there were signs of developmental delays early on, like he drooled too much, but we didn’t think much of it,” she said.

When he was 2, his doctor found that his blood lead levels were elevated, though they fell below the commonly defined threshold for effects of lead. Ten micrograms per deciliter has traditionally been defined as the harmful level, but recently the Centers for Disease Control and Prevention lowered it to five, recognizing that effects can occur at lower levels.

Synergy between lead and stress

With lead pollution, “the toxicity of lead may be stronger in a child also exposed to the stress of poverty,” said Dr. Robert Wright, a pediatrician and environmental health scientist at the Harvard School of Public Health, and husband of Rosalind Wright.

Lead exposure, which has been linked to reduced IQs, attention problems and aggressive behavior, may be more detrimental to low-income kids than to children in families with higher incomes. Children in Boston began to show reduced IQ at blood lead levels as low as six micrograms per deciliter, while kids from families with more financial resources only began to show cognitive deficits at levels greater than 10, according to one study.

“If this synergy exists between stress and lead, from a biological perspective, it’s plausible this link exists between stress and other neurotoxic pollutants, such as mercury and polychlorinated biphenyls (PCBs) as well,” said Robert Wright.

For years, toxicologist Deborah Cory-Slechta of University of Rochester and her colleagues have studied the combined effects of lead and stressful conditions on lab rats. Lead plus stress had effects on their learning ability and brains that did not occur with either of those factors alone, according to their research.

Researchers are trying to tease apart why chronic stress may make some pollutants more harmful. Both human and animal studies suggest that it can throw key systems of the body out of whack. At a young age, it may create hormonal shifts that permanently alter the way the body responds to future stresses, including chemical exposures. It also may weaken the immune system or trigger inflammation.

“Inflammation is central to a lot of chronic diseases we worry about today,” including respiratory diseases such as asthma, Clougherty said.

In one study, young male laboratory rats put under chronic stress showed a rapid, shallow breathing pattern when inhaling polluted air – unlike rats exposed only to the pollution.

The researchers created a stressful environment by placing the young male rat in the home cage of an older, dominant male twice a week. The stressed rats had higher levels of molecules associated with inflammation in their blood.

Also, in East Boston, children who were previously exposed to community violence were more likely to show signs of asthma when breathing traffic-related air pollution than children in less violent neighborhoods. “This suggests a model where stress impacts the child’s susceptibility to pollution,” said Clougherty.

In addition to asthma, this may make low-income children more predisposed to diabetes, heart disease and even dementia later in life.

Kids living with violence also may experience more wear and tear on their DNA, damage that has been linked to disease later in life, according to a Duke University study published in April.

Susceptibility starts in the womb. Exposure to stress and pollution before birth and during early childhood may be particularly harmful because “both may alter development of the brain, lungs and nervous system during these critical periods,” said Rosalind Wright.

This raises an important question: Are people protected by policies that just consider their chemical exposures without looking at their living conditions, too? Many scientists think not.

Increased risks due to social status are “a critically important but neglected area within risk assessment, and should be incorporated in the future,” Harvard epidemiologists Joel Schwartz and David Bellinger and Johns Hopkins’ Thomas Glass wrote in a 2011 report.

Schettler said “this new understanding has the potential to change the way we think about interventions for low-income children.”

More.

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Animation on how mice are used to study changes in DNA that could also occur in humans and eventually lead to cancer. The genetic similarity of mice to humans accounts for mice being a good experimental model to study cancer. Mouse models that mimic human disease play a vital role in understanding the etiology (cause and origin) of cancer. Results of mouse model studies lend evidence toward the next step in biomedical research that leads to early detection of cancer, new cancer drugs, new combinations of treatments, or new methods such as gene therapy.]

AIRS THIS THURSDAY, JAN 12

We’re fat. Really fat. Almost 60% of Canadians are now either overweight or obese, and that figure is expected to climb even higher. But what if we have an excuse?

In Programmed to be Fat?, we explore controversial new science that suggests being overweight is not just the result of too much food, too little exercise, and genetics.  Exposure to environmental chemicals such as Bisphenol A, pesticides and herbicides during fetal development may be changing our physiology forever. That, say some scientists, could explain the alarming statistics on obesity – like the fact that the number of overweight infants rose 74% in just twenty years.  Scientists are now moving beyond their mice and rat studies, to test the theory in people.  In Programmed to Be Fat?, we will get the skinny on the science of fat.

Premiering January 12, 2012 on CBC TV’s “The Nature of Things” with David Suzuki.

Directed by Bruce Mohun, written by Bruce Mohun and Helen Slinger, produced by Sue Ridout, Helen Slinger and Sara Darling.

Preview below:

From The Mail:

Growing up in a remote community on the west coast of Scotland in the Fifties, there was little opportunity for a boy with an embarrassing problem to discuss it with anyone.

‘You can imagine how people would have reacted,’ says Wilf Stevenson, 64, now Lord Stevenson of Balmacara. ‘It is not a subject easy to raise even now.’

Lord Stevenson, opposition whip and former special adviser to Gordon Brown, was born with hypospadias, a condition where the urethra, which delivers urine and sperm, comes out on the shaft of the penis rather than the tip. It does not necessarily affect urinary or sexual function, but it can make urinating difficult.

As Lord Stevenson explains, with some understatement: ‘Although the condition is as common as hare lip or cleft palate, it simply wasn’t talked about, and isn’t now. I just had to deal with it, and it wasn’t easy.’

He is among the one in 50 people (around 1.2 million Britons) thought to have been born with some kind of disorder of sexual development (DSD) as a result of errors in their genetic code.

These cause abnormalities while a baby is growing in the womb, and range from mild genital abnormalities to ‘intersex’ conditions such as congenital adrenal hyperplasia — where the baby has female and male physical characteristics such as a womb and a penis.

Overall, DSDs causing ‘ambiguous’ genitalia affect an estimated one in 1,000 people.

However, Lord Stevenson’s condition is more common — and it may be becoming increasingly so, as a result of ‘gender-bending’ chemicals used in plastics and hormones excreted by women taking the Pill or similar drugs used in animal rearing.

Although the use of growth promoting hormones is illegal in the EU and other countries, there may still be a risk in imported meat. Traces of these hormones have also been found in drinking-water supplies in studies by the Environment Agency and Medical Research Council.

‘There is no doubt that male reproductive disorders are increasing, but for some reason it is hard to get people to recognise the fact,’ says Professor Richard Sharpe of the Medical Research Council’s Centre for Reproductive Health at Edinburgh University, who runs a research group looking specifically at men.

‘It is an issue which ought to attract a great deal more attention,’ he says.
Professor Ieuan Hughes of Cambridge University, whose research focuses on abnormal sexual development in humans, says studies show a rise in the problem of undescended testes, where the organs remain within the body cavity of male babies, creating a risk of future infertility.

‘The latest research shows 7 to 8 per cent of babies are affected, and it was half that in the Sixties,’ he says.

More.

From the Chicago Tribune:

Pregnant women sacrifice many of life’s simple pleasures — caffeine, sushi, a glass of wine — in the hope that their baby will be born healthy.

But according to a provocative new field of research, what happens during pregnancy can have lasting consequences that emerge decades after the child leaves the hospital. Studies are finding that adult illnesses like heart disease, stroke, cancer and diabetes can have roots in the mysterious months we spend in the womb.

Although genetics and lifestyle choices certainly influence an adult’s risk of getting a disease, researchers now believe that the food a pregnant woman eats, her weight and fitness, her stress level, and the drugs, pollutants and infections she is exposed to can trigger changes that also make her baby vulnerable to disease after birth.

For example, scientists have found that a diet containing excessive protein can suppress fetal growth and lead to adult-onset hypertension. Expectant mothers who starved during their final trimester as a result of the Dutch famine of 1944-45 were more likely to have babies who later developed Type 2 diabetes. And the children of obese mothers also are at high risk of Type 2 diabetes and metabolic syndrome.

“Human beings break down the same reason cars break down; they’re either driven on bad roads or made badly in the first place,” said David Barker, a professor of clinical epidemiology at England’s University of Southampton, who in 1989 initially advanced the idea that coronary heart disease might originate in fetal life. “Some people are just strong and some are not. Being made bad means, biologically, that you have fewer functioning units.”

Experts stress that this field of study is relatively new and that the physical mechanisms that might explain the correlations between stressors in the womb and mechanical problems down the road are unclear.

It is also not lost on researchers that some pregnant women already are wracked with guilt over forgetting their prenatal vitamins or eating hot dogs instead of broccoli.

“I feel like a walking bomb,” said Chicago’s Amy Elstein, 28, who is five months pregnant and fears that her stress levels are affecting her baby. “It’s like my body is not my own. Everything I put into it — what I eat, what I breathe — I worry that will have an effect on my child.”

“Pregnancy feels like a period in your life when you want very badly to do the right thing, but you don’t have control of what’s going to happen, so women look for areas they can control,” said Dr. Ann Borders, an assistant professor of obstetrics and gynecology at Northwestern University. “We’re trying to help women be aware of unhealthy stresses but not freak out that they’re hurting baby for long term.”

The current advice for pregnant women still stands: Eat nutritious foods, exercise, reduce stress and avoid smoking and drinking.

But Barker and other scientists in the field want to step up prenatal care radically because they believe the diets of girls and young women are determining the health of the next generation.

Eventually, this area of research “will make a huge impact on not just what we tell women during pregnancy, but what our children’s health will be,” said Alan Guttmacher, director of the National Institute of Child Health and Human Development.

It was once widely assumed that, aside from cigarette smoke, drugs and excessive alcohol, the uterus, or womb, sheltered the fetus from environmental influences. Scientists also thought that the growing fetus could siphon off necessary nutrients from a mother like a parasite to ensure its survival.

Two decades of research into the fetal origins of disease, however, have challenged both assumptions and led to a revolutionary shift into the thinking about health and development.

According to Barker’s widely accepted fetal origins theory, also referred to as the developmental origins of health and disease, stressors in the womb can permanently change a fetus’s body structure, physiology and metabolism. Those changes then can lead to a higher risk of illness in the future.

More.

(Image from Flickr.)

From the Montreal Gazzette:

Early childhood living conditions provoke biological changes in genes leading to DNA “memory” that can last a lifetime, an international study has found.

Experts have already noted that income, education and neighbourhood resources can have a dramatic effect on children’s health, and that a poor socio-economic environment in infancy can translate into a higher risk of adult disease and early mortality.

But a study published online Thursday in the International Journal of Epidemiology suggests that early experience works changes that are far more than skin deep.

The environment of early childhood influences brain and biological development and leaves a “memory” in the genetic code that affects the way genes function, say researchers from McGill University, the University of British Columbia and the UCL Institute of Child Health in London, England.

“Biological embedding” may help explain why health disadvantages linked to a lower socio-economic origin — including obesity, mental health problems, heart disease, diabetes and other chronic illnesses — can last a lifetime even if living conditions improve later.

The team focused on a small sample — 40 men — from the ongoing British cohort study, which has followed 10,000 people born in March 1958 from birth onward.

The team looked at the DNA of men aged 45 who came from one of two economic extremes: children whose fathers were unskilled workers; and those whose dads were company CEOs and Oxford/Cambridge graduates.

“We wanted to sample from the extremes so that if there was an epigenetic (gene) signal, it would be as clear as possible — and that’s in effect what emerged,” said Clyde Hertzman, director of the UBC-based Human Early Learning Partnership and an author of the study.

After looking at control areas of 20,000 genes, researchers found twice as many genetic differences (1,252 changes) in those brought up in wealth and comfort compared to those raised in poor living conditions (545 changes), making a link between the economics of early life and the biochemistry of DNA.

More.

From Leadership:

Why are some people predisposed to being anxious, overweight or asthmatic? Why are some of us prone to heart attacks, diabetes or high blood pressure? You may say it’s our genes. Or our childhood experiences: How we were treated especially during those crucial first three years. Or maybe our well-being stem from lifestyle choices we make as adults, like our diet and how much exercise we get.

But what about your life in the womb? The nutrition you received; the pollutants, medicines and infections you were exposed to; your mother’s health, stress and state of mind while she was pregnant with you – pioneers in the controversial field of fetal origins say these factors shaped you as a baby – and for the rest of your life.

They assert the nine months in the womb permanently influence the wiring of the brain, the functioning of organs such as the heart, liver and pancreas, how prone we are to disease, our appetite and metabolism, our intelligence and temperament.

Much of what a pregnant woman encounters in her daily life – the air she breathes, the food and drink she consumes, the chemicals she’s exposed to, even the emotions she feels – are shared with her fetus. It incorporates these into its own body, making them part of its flesh and blood.

Research on fetal origins, also called the developmental origins of health and disease, is prompting revolutionary shifts in thinking about where human qualities come from and when they develop.

* * *

Two decades ago, a British doctor named David Barker noticed an odd . pattern on a map: The poorest regions  of England and Wales had the highest rates of heart disease. But heart disease was supposed to be due to a sedentary lifestyle and rich food?
After comparing the health of 15,000 adults with their birth weights, he discovered an unexpected link between small birth size, often an indication of poor prenatal nutrition, and heart disease in middle age.

Dr Barker theorized that when a fetus does not get enough nutrition, it diverts nutrients to the brain, while skimping on other parts of its body. This shows up in later life as a weaker heart.

When he presented his findings to colleagues, he was mocked. “Heart disease was supposed to be all about
genetics or adult lifestyle,” says Dr Barker, now 72, and a professor at the University of Southampton in  England and at Oregon Health and Science University. “People scoffed at the idea that it could have anything to do with intrauterine experience.”
For years, the idea was just known as the Barker hypothesis. But in time, it began to win converts. Dr Janet Rich-Edwards, an epidemiologist at Brigham and Women’s Hospital in Boston analysed findings from the Nurses’ Health Study, a long-running investigation of more than 120,000 nurses in the US.

* * *

The good news is that fetal researchers are also finding out that life in the womb can make things go better for your child in later life.

* * *

Take your weight. Two studies by researchers at Harvard Medical School suggest your mother’s weight affects  yours. One study found that the more weight a woman gains during pregnancy, the more likely her child is to be overweight by age three.

* * *

“The bodies of the children conceived after their mothers had weight-loss surgery process fats and carbohydrates in a healthier way than the bodies of their brothers and sisters  who were conceived at a time when their mothers were still overweight,” says John Kral, a professor of surgery and medicine and a co-author of both papers.

“It may be the intrauterine or womb environment is more important than genes or shared eating habits in passing on a tendency to be obese,” says Professor Kral. If that’s so, helping women maintain a healthy weight during pregnancy may be the best hope for stopping obesity before it starts.

* * *

How does air pollution affect a baby in the womb? More than 30 years ago, [Upstream Contributor] Dr. Frederica Perera, the director of the Center for Children’s Environmental Health at Columbia University, was researching air pollution and cancer in adults. “I was looking for control subjects to compare to adults. I wanted individuals completely untouched by pollution,” she says.

She decided to use babies just out of the womb as her controls. So she sent samples of umbilical-cord blood and placental tissue to a laboratory to be analysed. When she got the results back, “I was shocked. These samples already had evidence of contamination.”

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[Upstream Contributor] Dr. Frederica Perera touches on how the environment around us can make a big impact very early in life and stick with us for a long time. This short take was shot during a break at Keystone Symposia’s meeting on Environmental Epigenomics and Disease Susceptibility held in March 2011 in Asheville, North Carolina.

 

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