[Pharmwaste] Epigenetics

Wed Oct 18 11:08:20 EDT 2006

http://www.precaution.org/lib/06/prn_stop_the_killing.pt1.060921.htm
Rachel's Democracy & Health News #876, October 12, 2006

SOME CHEMICALS ARE MORE HARMFUL THAN ANYONE EVER SUSPECTED

By Peter Montague

New evidence is flooding in to suggest that many industrial chemicals
are more dangerous than previously understood. During the 1990s, it came
as a surprise that many industrial chemicals can interfere with the
hormone systems of many species, including humans. Hormones are
chemicals that circulate in the blood stream at very low levels (parts
per billion, and in some cases parts per trillion), acting like
switches, turning on and off bodily processes. From the moment of
conception throughout the remainder of life, our growth, development and
even many kinds of behavior are controlled by hormones.

Now new evidence is piling up to show that some of these hormone-related
changes can be passed from one generation to the next by a mechanism
that remains poorly understood, called epigenetics.

Until very recently scientists had thought that inherited traits always
involved genetic mutations -- physical changes in the sequence of
nucleotides that make up the DNA molecule itself. Now they know that
there is a "second genetic code" that somehow influences the way genes
operate, and that by some poorly-understood mechanism can be passed
along to successive generations.

Medical scientists hope to take advantage of the new science of
epigenetics to manipulate the behavior of genes for beneficial purposes.
But the dark side of this new understanding is that stress, smoking, and
pollution can cause epigenetic changes -- including many serious
diseases like cancer and kidney disease -- that apparently can be passed
along to one's children and even grandchildren. For example, Dutch women
who went hungry during World War II gave birth to small babies. These
babies, in turn, gave birth to small babies even though they themselves
had plenty to eat. "It changes the whole way we think about
inheritance," says Dr. Moshe Szyf at McGill University in Toronto.

Just last month professor Michael Skinner at Washington State University
in Spokane announced results of laboratory experiments
<http://www.precaution.org/lib/06/prn_cancer_toxin_connection.060915.htm
>  showing that environmental pollution could permanently reprogram the
genetic traits of a family line of rodents, creating a legacy of
sickness. This research "highlights the long-term dangers from
environmental pollution," professor Skinner said. Dr. Skinner showed
that a single exposure to a toxic chemical in the womb could produce a
sick litter of offspring, which in turn could produce its own sick
offspring. "It's a new way to think about disease," Dr. Skinner said.

"A human analogy would be if your grandmother was exposed to an
environmental toxicant during mid-gestation, you may develop a disease
state even though you never had direct exposure, and you may pass it on
to your great-grandchildren," Skinner said.

"It introduces the concept of responsibility into genetics," says Dr.
Szyf. As a recent story
<http://www.precaution.org/lib/06/prn_code_2.060311.htm>  in the Toronto
Globe & Mail summarized, "Epigenetics may revolutionize medicine, said
Dr. Szyf, and it also could change the way we think about daily
decisions like whether or not to order fries with a meal, or to go for a
walk or to stay in front of the television. You aren't eating and
exercising for yourself, but for your lineage."

On average, 1800 new chemicals are registered with the federal
government each year and about 750 of these find their way into
products, all with hardly any testing for health or environmental
effects.

Brominated flame retardants, phthalates, bisphenol-A, PFOA (related to
the manufacture of Teflon) are the toxins that have gained our attention
at the moment. By working overtime for 10 or 15 years in the traditional
environmentalist way, we may be able to ban a half-dozen of them. But
during that 10 or 15 years, the chemical industry (and the federal EPA)
will have introduced somewhere between 7,000 and 10,000 new chemicals
into commerce, almost entirely untested. This destructive merry-go-round
is accelerating.

Faced with evidence of harm, governments tend to respond initially by
conducting "risk assessments" to show there is no problem. The main
function of risk assessment is to make chemical problems disappear,
almost like magic. As EPA's first administrator, William Ruckelshaus,
reminded us, "We should remember that risk assessment data can be like
the captured spy: If you torture it long enough, it will tell you
anything you want to know."

So the bad news about chemical contamination is steadily mounting, while
the number of new chemicals is steadily increasing. As we have been
reporting regularly in Rachel's Precaution Reporter
<http://www.precaution.org/lib/06/ht061011.htm> , the European Union has
responded to this situation by trying to enact a new law called REACH,
which requires that chemicals be tested before they can be sold. As they
say in Europe, "No data, no market." The U.S. and European chemical
industries -- and the White House -- have been working overtime to
subvert the European effort to enact REACH. But now it looks as though
REACH -- in one form or other -- will become law soon. It will be
binding on any corporations that want to sell chemicals in Europe,
including firms based in the U.S.

Rachel's Democracy & Health News #876
"Environment, health, jobs and justice--Who gets to decide?"
Thursday, October 12, 2006..............www.rachel.org
<http://rachel.org> 

************
http://www.precaution.org/lib/06/prn_code_2.060311.htm
Globe & Mail (Toronto, Ontario), March 11, 2006

CODE 2

[Rachel's introduction: Scientists are still deciphering what has been
described as the second genetic code. They know that a number of
chemicals in our bodies act like dimming switches. They suspect this
chemical switching system can be affected by diet, the air pollution we
inhale, whether we smoke, and the stress we endure -- and the resulting
changes can be passed along to offspring.]

By Anne Mcilroy

Scientists are rewriting the laws of heredity as they learn more about a
mysterious second genetic code that turns our genes on and off.

The traditional idea that we are the passive carriers of our genes is
being challenged by the notion that we are their custodians. Our
lifestyles -- what we eat, how much we exercise, whether we smoke -- may
play a role in a chemical switching system that activates or deactivates
our genes. There are signs that our behaviour may program sections of
our children's DNA, and that how we live may even affect our
grandchildren's genes.

"It introduces the concept of responsibility into genetics," said Dr.
Moshe Szyf, a researcher at McGill University in Montreal and a pioneer
in the field of epigenetics, the study of genetic changes that don't
involve mutations in DNA.

"It changes the whole way we think about inheritance."

If DNA is the hardware of inheritance, the epigenetic operating system
is the software, controlling the 30,000 genes that carry instructions
for the proteins that make up our bodies and keep them running.

Scientists are still deciphering what has been described as the second
genetic code. They know, Dr. Szyf said, that a number of chemicals in
our bodies act like dimming switches and determine whether every gene in
each cell produces a lot of a particular protein, very little or none of
it.

They suspect this chemical switching system can be affected by diet, the
air pollution we inhale, whether we smoke, and the stress we endure. It
may be a mechanism through which our environment affects our genes.

In mice there is proof some of these changes can be passed down from
generation to generation. There are signs this may be the case for
humans, as well, if the environmental changes affect genes in sperm or
eggs.

A recent study found that found men who started smoking before puberty
are more likely to have overweight male children. Dutch women who went
hungry in the Second World War gave birth to small babies, but their
children also had small babies, even though they had enough to eat.

There is also evidence, at least in rats, that a mother can turn genes
on and off in her offspring. Mothers who lick their pups activate a gene
that restricts the production of the stress hormone cortisol. As a
result, their babies are more laid back.

Canadians scientists in Montreal and Hamilton are now doing an
unprecedented experiment in humans, and want to find whether a mother's
behaviour affects similar genes in young children. They should have
preliminary results by the fall.

A recent study in Spain found that as identical twins get older, they
become genetically less similar. They start out with the same genes, but
as they age, the switches that control their genes start to look
different. The changes are barely noticeable in three-year-old twins,
and most pronounced in elderly twins, especially those who have spent
less of their lives together.

This helps explain why, in the Spanish study, a 35-year-old woman
developed breast cancer but her identical twin didn't. It may also
explain why when one identical twin develops schizophrenia, it is
estimated that the other one has only a 50-per-cent chance of developing
the mental illness.

Pamela Spiro Wagner started hearing voices the day John F. Kennedy was
assassinated. Carolyn Spiro, her identical twin, became a psychiatrist.
She was on call at a Boston hospital when her sister was admitted in a
catatonic state, one arm extended into the air.

"This can't be my twin," she recalls thinking at the time. The two wrote
a memoir, published last year, called Divided Minds: Twin Sisters and
their Journey through Schizophrenia.

Identical twins can look less similar as they get older, and often act
very differently. Epigenetics may help explain why.

Connie Millar, 31, says she began noticing more physical differences
between herself and identical twin Kendra four or five years ago.

The sisters share a home in Welland, Ont.

"My hair is nice and full," Connie said. Kendra, younger by 11 minutes,
conceded her hair is little thinner.

"Hers is more curly."

Their noses are a little different. Connie's turns up a little more,
Kendra said. Connie weighs about 30 pounds less than her twin, and likes
to curl and dance and go to the racetrack. Kendra is more of a homebody,
and is fascinated by royalty.

Darrick Antell, a plastic surgeon in Manhattan, began doing face lifts
on identical twins so he could compare the two surgical techniques. But
he found that one twin was always an older version of the other.
Smoking, sun exposure, diet and the amount of stress they had endured
took a toll on their faces. But some of the differences were not so
easily explained. One set of twins lived together, but one smoked and
the other didn't. The smoker had much more grey hair than his twin.

"I think there is more at work here," said Dr. Antell, who has performed
plastic surgery on more than 30 sets of twins, more than anyone else in
the world.

But epigenetics may help explain more than the differences between
people who are genetically identical.

Scientists are also looking at many common diseases to see if they might
be caused, at least in part, by problems with the switching system that
activates and deactivates genes. In Canada and around the world
researchers are looking at the role epigenetics plays in various kinds
of cancer, schizophrenia, bipolar disorder, Parkinson's disease,
Alzheimer's disease, lupus and other illnesses.

Genes seem to play a part in all of these diseases, but not always the
starring role. One patient with Alzheimer's can't recognize the faces of
their loved ones, while someone else with the same gene linked to the
disease is lucid at the age of 90.

The difference is not a mutation, or a change to the four chemicals --
known as nucleotides -- that make up the long strings of DNA in our
chromosomes that we inherited from our parents. The problem may be an
aberration in the operating system that controls which genes are turned
on and off, and how much protein they produce.

In a number of kinds of cancer, a gene that suppresses tumour growth
appears to get turned off, Dr. Szyf said. He and his colleagues believe
they have discovered a way to turn it on again, with one of two
epigenetic cancer drugs now being tested in clinical trials by the
Montreal company MethylGene.

They aren't alone. Researchers say dozens of new epigenetic cancer drugs
are now being tested around the world, almost all attempting to turn on
genes that stop the growth of tumours. One, azacitidine or Vidaza, has
been approved in the United States, but not yet in Canada. So far,
however, it is not a miracle drug. It appears to help 16 per cent of
those who take it.

Dr. Szyf is also exploring what role the switching system plays when
cancer metastasizes, or spreads from the original site to other parts of
the body.

He is also interested in the role gene switches play in behaviour,
including suicide. He is working on epigenetic profiles of men who
committed suicide, studying cells from their brains to see if there is a
pattern in the genes that are turned on or off. So far, he has studied
cells from 14 men who killed themselves, and says the preliminary
results are promising.

Arturas Petronis, at the Centre for Addiction and Mental Health in
Toronto, is working on the epigenetic profiles of both schizophrenia and
bipolar disorder, which used to be known as manic depression. He is
studying the brain cells of people with those mental illnesses who died,
and comparing them with cells from the brains of people who didn't have
either disease. He is looking for a pattern of on-off switches that is
distinctive in schizophrenia and in bipolar disorder.

There is no evidence that lifestyle factors -- like drug use -- play a
role in switching genes on or off in people who suffer from mental
illness. Neither is there proof that lifestyle causes epigenetic changes
that lead to other diseases, like cancer. But it may that be that
smoking, for example, alters the activity of genes in lung cells.

Dr. Petronis characterizes the epigenetics explanation as a promising
theory, one that may answer many perplexing questions about cancer and
other diseases.

But first, he and other researchers caution, many mysteries need to be
solved. No one knows how the switches in all our cells are controlled.
Also unknown is to what extent changes in them are passed down from
generation to generation.

Some researchers, however, believe epigenetics holds enormous promise
for treating disease. It may be possible -- eventually -- to turn genes
on or off, to increase or decrease the production of protein that is
part of a disease. It may prove easier than conventional gene therapy,
where new genes are inserted into a patient's genetic code.

"Epigenetics will completely change the face of medicine," Dr. Szyf
predicted.

It also may change the way we think about pollution, or the chemicals in
many products we use every day.

A number of scientists suspect that heavy metals, pesticides, diesel
exhaust and tobacco smoke and other chemicals in the environment may be
interfering with the human genetic switches. They fear that endocrine
disrupters, the so-called gender-bender chemicals, may somehow be
switching genes on and off, resulting in fish with both male and female
sexual organs and male alligators with shrinking penises.

Michael Skinner a professor at Washington State University, briefly
exposed pregnant rats to high levels of two endocrine disrupters, and
insecticide and a fungicide. He and his colleagues found that their male
offspring had lower fertility and sperm production for not one, but four
generations.

Dr. Syzf said that in the future, chemicals should be evaluated not only
for whether they cause changes to DNA, but whether they affect the
amount of protein a gene produces.

He is working on a way to do this, and said the first step is to
identify the sites in the genome that are most vulnerable to these
changes.

Scientists are also intrigued about the role epigenetics may play in
evolution. Switching genes on and off may be a way for animals,
including humans, to adapt to the environment more rapidly than the
glacial speed allowed by evolution, which depends on relatively rare
mutations to DNA.

"You inherit DNA, but it doesn't tell you if you are living in a rich or
a poor environment. If it is rich, you don't have to store fat, don't
need to be anxious," Dr. Szyf said. "But if you are going to be thrown
in a ghetto, that is a different thing."

Take the mother rats that don't lick their pups much. They tend to be at
the low end of the rat social hierarchy, and as a result lead more
stressful lives. It is probably a good thing that their pups produce
more cortisol -- a stress hormone -- and are more uptight. Cortisol
makes rats less aggressive, and less likely to get into fights they
can't win.

Researchers in Montreal have found that the boys in neighbourhoods with
high crime rates who don't get in much trouble tend to have higher
levels of cortisol than boys who join gangs or steal cars. Their higher
stress level seems to make them more fearful, and less likely to engage
in risky business.

As for our modern lifestyles, exercise is good, but not just for burning
calories. It may reprogram our genes, Dr. Szyf said.

Fat may do more than add extra body weight and clog arteries; it may
also switch a number of genes on and off that in the past were helpful
in preparing humans for a long winter without much food.

Epigenetics may revolutionize medicine, said Dr. Szyf, and it also could
change the way we think about daily decisions like whether or not to
order fries with a meal, or to go for a walk or to stay in front of the
television. You aren't eating and exercising for yourself, but for your
lineage.

Loosening the strands of DNA

Flicking genes on and off.

It would mean chaos -- and probably death -- if every gene in every cell
of our body were active at once. Brain cells would get clogged with the
proteins the kidneys, liver, heart, lungs and skin need to function, and
vice versa.

The body needs a way to orchestrate our genes -- especially when an
embryo is developing. Scientists are learning more about the chemical
switching system that determines what genes get turned on or off, and
when.

Most genes carry instructions about what cells they will be used in,
says Tom Hudson, a researcher at McGill University in Montreal. But they
still need to be activated or deactivated.

Scientists know that for easy storage, the DNA in cells is tightly
wrapped around blocks that are called histone proteins. Think of string
around a grapefruit, says Michael Meaney, a McGill researcher who found
that mother rats can turn a gene on in their pups by frequently licking
them.

For a gene to work, and make a protein, the string has to loosen, or the
grapefruit has to move or change shape. So far, scientists know of at
least five ways this happens, and are exploring how the different
chemical reactions that turn genes on and off may be linked. The process
they perhaps understand the best is called methylation, in which
chemical tags are added to the DNA, tightening the string around the
grapefruit so that a gene is silenced, or partially silenced.

Scientists are now mapping these tags, much as they mapped the human
genome. They are marshalling resources for an international effort,
similar to the human genome project. So far, scientists have mapped the
differences in 25 genes that suppress the growth of tumours, says Manel
Esteller, a Spanish researcher who did an experiment that showed
identical twins become less genetically similar as they age.

They say the human epigenome project will produce profiles of diseases,
a map that would show which genes are turned on or off in people with
various forms of cancer, as opposed to people who don't get the disease.

Canadian researchers are working on their own on similar epigenetic
profiles of schizophrenia, bipolar disorder and other diseases.

It most cases, it seems that epigenetic changes are not passed from
parents to their offspring. Scientists aren't sure how -- but genes
seems to be wiped clean after a sperm fertilizes an egg.

But they are intrigued by the notion that some changes may be passed on
from generation to generation, and may be influenced by our diet or
behaviour.

There is proof this sometimes happens in plants, yeast flies and
mammals. Researchers in Australia and the U.S can get yellow mice to
have brown babies if they feed them nutritional supplements like folic
acid and vitamin B12 during pregnancy. But genetically identical yellow
mice not given the supplements had yellow babies.

All of the animals had the same gene that helps determine fur colour,
known as the Agouti gene. But in the mothers who were fed the dietary
supplement -- and their babies -- the gene had extra chemical tags
attached. It was methylated, and produced much less of the protein that
colours mouse hair.

It has not been proven that changes to the epigenetic switching can be
passed from generation to generation like this in humans, but there are
signs it may happen, especially as it relates to diet. Swedish
researcher Gunnar Kaati and his colleagues have looked at records from
1890 to 1920. They found that boys who matured in times of plenty had
grandchildren with a higher rate of diabetes.

Deborah L. DeBiasi
Email:   dldebiasi at deq.virginia.gov
WEB site address:  www.deq.virginia.gov
Virginia Department of Environmental Quality
Office of Water Permit Programs
Industrial Pretreatment/Toxics Management Program
Mail:          P.O. Box 1105, Richmond, VA  23218 (NEW!)
Location:  629 E. Main Street, Richmond, VA  23219
PH:         804-698-4028
FAX:      804-698-4032