Soiled Genes: Can toxic exposures be inherited?
Leslie A. Pray
Source: OrionOnline, the website of Orion Magazine,
http://www.oriononline.org/pages/om/05-6om/Pray.html
On my wall is a framed black-and-white photograph from
the turn of the nineteenth century. A young girl, my
mother's mother, stands surrounded by her three older
sisters and my great-grandmother, Margaret Hunter. All
five look bemused, each about to crack a smile, as
though at any moment they might come alive. They are
taking a day for play away from their labor-intensive farm
life. Margaret and husband Joe raised their four girls
and five boys in the vast waving prairie land of
Saskatchewan.
These are the foods I imagine they ate: chicken and
dumplings, pheasant and quail and game of all sorts,
wild mushrooms, Saskatoon berry pie, and lots of
bread-sugary breads, pan-fried bread dough, bread smothered
with chokeberry spread.
I have looked at this photo of my maternal ancestors
many times, and I have wondered many things. But it
only occurred to me recently to question the culinary
legacy of my inheritance and the bounty of the land that
nurtured my recent genetic stock. How might the
century-old diet of my mother's people be affecting my
health today? And it's not just the food that I wonder
about. What about the air they breathed, the water they
used for bathing, the materials they smelled and touched
and absorbed through their skin-might any of those
environmental exposures have lingering effects on my
health? I ask because scientists have stumbled recently on
some remarkable clues that suggest that we inherit
more than our ancestors' genes. We also inherit, in a
very real, physical, molecular way, their environment-not
through our genes but through our epigenomes.
Derived partially from the Greek prefix epi-, which
means "on" or "in addition," the epigenome is to the
cell what an organism's sensory organs are to the
individual. Like an octopus's tentacles that, among other
functions, gather information from the environment so
that the brain can tell the neurons, "Move your eighth
arm here," the epigenome gathers information from the
cell's environment and tells the genes, "turn on" or
"turn off." In science lingo, it governs "gene
expression." Based on emerging evidence, the epigenome appears
to play a vital role in most, if not all, cellular
activity, from metabolism to fertilization.
Imagine the genome: each of our cells has a set of
some twenty to thirty thousand genes, each gene composed
of hundreds to thousands of DNA-based compounds strung
together like rungs on a ladder. The DNA compounds are
organized into what has been famously called the
double helix, a twisted ladder of molecules occupying our
every cell, governing our body's every move. Now
imagine this: attached like side rungs to the DNA ladder are
millions of methyl molecules, each consisting of a
single carbon and three hydrogen atoms. The clusters of
methyl molecules act like sensors, interpreting the
environment, throwing switches.
Along with some other lesser-known chemical
modifications, this genome-wide pattern of methyl switches is
the epigenome, which is as important to the healthy
functioning of a cell as the DNA itself. A gene turned on
or off at the wrong time can wreak molecular havoc. In
just about every kind of tumor cell ever studied,
genes known as tumor suppressor genes, which normally
prevent the growth of tumors, are mistakenly silenced when
too many methyl molecules attach themselves to the
gene. Abnormal methylation patterns have also been linked
to such conditions as diabetes, obesity, autoimmune
diseases, and psychiatric diseases.
Although the mechanics haven't been thoroughly
studied, it appears that abnormal methylation patterns result
when the epigenome responds to unusual environmental
signals. The epigenome is where our genes interface
with the environment, reading and interpreting hormones,
nutrient levels, and electrical and other signals in
ways that enable the cell-and the organism-to respond
appropriately to change and in ways that the genome
alone cannot. Turning a gene on or off is a much faster
way of adapting to an environment than natural
selection is; adaptation can happen over the course of a
lifetime. That can be a good thing. In 2003, scientists
from Duke University showed that feeding mice unusually
large amounts of nutritional supplements caused certain
genes to become abnormally overmethylated, decreasing
the animal's ris k of cancer, diabetes, and other
health problems. But it can also mean, as with turned-off
tumor suppressors, that things can go wrong during a
lifetime.
Because the epigenome can respond so quickly to
chemical and electrical changes in the cellular environment,
individuals born with one epigenome will likely die
with another. In a study published by the National
Academy of Sciences in July 2005, researchers reported
dramatic epigenomic divergence between genetically
identical human twins, each twin accumulating over time its
own unique set of methylation mutations. The twin study
helps explain why genetically identical individuals
who grow up in different environments develop different
health problems.
Researchers have known for decades that the epigenome
exists. But for years, all eyes were on the genes,
says Richard Strohman, professor emeritus of microbiology
at University of California, Berkeley. "If you have a
new idea that contrasts with or is critical of the
main pattern of belief," says Strohman, "you won't be
listened to." But in the last twenty years investigators
have uncovered enough molecular detail to convince the
scientific community at large that the epigenome
matters. And within the last five years geneticists have
uncovered enough evidence about the epigenome's
environmental sensitivity from experiments like the twin study
to cautiously raise a fundamental question: when it
comes to human health, might the environment matter more
than our genes?
The question has taken on new gravity in light of
evidence, reported in the June 2005 issue of Science
magazine, that epigenetic change can be inherited.
Researchers from Washington State University showed that
pregnant rats exposed to pesticides not only suffered
epigenetic damage but also passed it down three
generations, to the great-grand-offspring. More than 90 percent
of male offspring, across all three generations, were
born with infertility problems, all of which were due
to that initial pesticide exposure. The study did not
report which abnormal methylation pattern or other
chemical modifications to the genome might have caused the
inherited toxin damage, but it did rule out DNA
mutation.
The Washington State study corroborates at least two
earlier studies, involving mice and fruit flies, that
found that epigenetic change could be inherited. Taken
together, the evidence lends credence to the
controversial theory of eighteenth-century naturalist Jean
Baptiste de Lamarck, who argued that organisms acquire
useful traits during their lifetimes and pass them on to
their offspring.
I doubt, perhaps naïvely, that my great-grandmother's
and my grandmother's epigenomes suffered much
environmental harm, living as they did off the land, before
the beginning of the chemical onslaught that we know
today. But what of their London-bred forbears? Did the
belching coal smoke, the soot, the stench-filled sewage
of the Thames cause epigenetic change? If so, was it
passed down and ferried through the germ line, across
the Atlantic, to my mother's family and eventually to
me?
More importantly, what have I and my siblings
consumed, touched, and breathed, and how will it affect our
children and grandchildren and great-grandchildren? The
epigenome's role as environmental sensor should give
us cause to think about environmental health in a
different way. Science has now provided evidence that when
organic solvents and other toxic chemicals are
released into the air we breathe, the water we drink, the
soils that grow our food, it is our progeny who inherit
the results. If nothing else, this serves as a helpful
reminder to think less of ourselves, and more of our
genetic heritage-"our link with the past and future,"
as Rachel Carson put it, "a possession infinitely more
valuable than individual life."
Leslie A. Pray, a biologist and educator, writes
policy reports for the Board on Global Health at the
National Academy of Sciences. Her work has appeared in the
Chronicle of Higher Education, Next Wave, The
Scientist, Wild Earth, and other publications. She lives in
Western Massachusetts.
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