by Tom Paulson, Seattle Post
It's just a study involving a few rats with fertility problems
in Pullman, but the findings could lead to fundamental changes
in how we look at environmental toxins, cancer, heritable diseases,
genetics and the basics of evolutionary biology.
If a pregnant woman is exposed to a pesticide at the wrong time,
the study suggests, her children, grandchildren and the rest of
her descendants could inherit the damage and diseases caused by
the toxin -- even if it doesn't involve a genetic mutation.
"As so often happens in science, we just stumbled onto this,"
said Dr. Michael Skinner, director of the center for reproductive
biology at Washington State University.
Skinner's team at WSU and colleagues from several other universities
report in today's Science magazine on what they believe is the
first demonstration and explanation of how a toxin-induced disorder
in a pregnant female can be passed on to children and succeeding
generations without changes in her genetic code, or DNA.
"We were quite surprised ... we've been sitting on this
for a few years," said Skinner, who is expected to present
his findings today at a scientific meeting in San Diego.
The report in Science, entitled "Epigenetic Transgenerational
Actions of Endocrine Disruptors and Male Fertility," also
sounds like an attempt to avoid attention. That's unlikely to
work. The findings prompt serious and, in some cases, disturbing
questions about a number of basic assumptions in biology.
The standard view of heritable disease is that for any disorder
or disease to be inherited, a gene must go bad (mutate) and that
gene must get passed on to the offspring.
What Skinner and his colleagues did is show that exposing a pregnant
rat to high doses of a class of pesticides known as "endocrine
disruptors" causes an inherited reproductive disorder in
male rats that is passed on without any genetic mutation.
It's not genetic change; it's an "epigenetic" change.
Epigenetics is a relatively new field of science that refers to
modifying DNA without mutations in the genes.
"It's not a change in the DNA sequence," Skinner explained.
"It's a chemical modification of the DNA."
Scientists have known for years about these changes to DNA that
can modify genes' behavior without directly altering them.
One form of epigenetic change is natural. Every cell in the body
contains the entire genetic code. But brain cells must use only
the genes needed in the brain, for example, and kidney cells should
activate only the genes needed for renal function.
Cells commonly switch on and off gene behavior by attaching small
molecules known as methyl groups to specific sections of DNA.
The attachment and detachment of methyl groups is also an important
process in fetal development of the male testes and female ovaries
-- which is where Skinner got started on this.
But the common wisdom has been that any artificially induced
epigenetic modifications will remain as an isolated change in
an individual. Because no genes get altered, the changes cannot
be passed on.
"We showed that they can be," Skinner said.
The experiment got its start four years ago by accident. His
lab was studying testes development in fetal rats, using a fungicide
used in vineyards (vinclozin) and a common pesticide (methoxychlor)
to disrupt the process. A researcher inadvertently allowed two
of the exposed rats to breed, so the scientists figured they'd
just see what happened.
The male in the breeding pair was born with a low sperm count
and other disorders because of the mother's exposure to toxins.
No surprise. But the male offspring of the pair also had these
problems, as did the next two generations of male rats.
"I couldn't explain it," Skinner. This wasn't supposed
to happen. The scientists didn't tell anyone about their finding
and continued, for the next two years, to confirm that it was
real and to find an explanation. Eventually, they documented that
a toxin-induced attachment of methyl groups to DNA in the mother
rat was being passed on to offspring.
"In human terms, this would mean if your great grandmother
was exposed to an environmental toxin at a critical point in her
pregnancy, you may have inherited the disease," Skinner said.
While the study was focused on a heritable disorder of reproduction
in rats, he said there's every reason to believe this can happen
for other diseases -- such as cancer.
"There has been this speculation that the increased rates
of some cancers may be due to environmental factors, but they've
never been able to describe a mechanism to explain this,"
The findings also suggest a reconsideration of one of the basic
tenets of evolutionary biology -- that evolution proceeds by random
The standard view is that the environment has no direct influence,
except in how it may favor or discriminate against the creatures
with the latest genetic mutations.
The WSU study, Skinner said, suggests the possibility that environmental
factors such as toxins may also directly cause heritable changes
in creatures. "Epigenetics may be just as important as genetics
in evolution," he said.