neuroimmune disease, the work of Dr. Skinner may have implications in these
fields also. For example, researchers already know that the herpes virus,
HHV-6A, and possibly some retroviruses, can in some instances insert
themselves into the host DNA. The genetic implications of viruses are being
done in studies regarding cancer and neuroimmune diseases by such
researchers as Dr. Jonathan Kerr and Dr. Dharam Ablashi. Although much work
remains to be done - it may well be most likely be done by researchers like
Skinner who think outside the box.
This Just In: More Research Needed
By: Valerie Brown <javascript:print();>
The question of whether prenatal environmental influences can affect
patterns of disease throughout life =97 and whether the influence affects
genes themselves or their epigenetics (the complex structures that package
and protect the DNA in every cell) =97 continues to vex scientists, parents
and regulators.
In the last few years, there has been an explosion of research confirming
the broad principle that events such as maternal stress, nutritional
deficits and chemical exposures in the womb can spell trouble for an
organism, sometimes many years into adulthood. But how much is passed on to
following generations, and for how many generations?
In 2008, *Miller-McCune* reported on research by molecular biologist Michae=
l
Skinner of Washington State University and his colleagues that showed
prenatal chemical exposure caused reproductive and other damage through the
fourth generation following maternal dosing with the fungicide vinclozolin
and the insecticide methoxychlor. Vinclozolin inhibits proper functioning o=
f
male hormones, and methoxychlor does the same to female hormones.
In September, Miller-McCune.com reported that other scientists, including a=
n
Environmental Protection Agency researcher and two others who work for the
manufacturers of the two chemicals, have been unable to replicate Skinner's
results and therefore challenge his claims of multigenerational transmissio=
n
of environmentally induced damage.
Most researchers in the field concede that epigenetic changes can persist
through at least two and probably three generations =97 the exposed mother,
the exposed fetus and the offspring of the exposed fetus (because the eggs
or sperm of the exposed fetus would also be exposed). But Skinner says he
has seen reproductive problems, cancers and other diseases in the generatio=
n
after that =97 with no direct exposure to the original toxic substance.
The stakes of the dispute over Skinner's findings are very high. If correct=
,
Skinner's results will have profound implications for chemicals regulation,
prenatal care, nutrition and the management of chronic diseases and
disorders that appear late in life. They would also illuminate phenomena
affecting inheritance and therefore shed light on evolutionary processes. I=
f
Skinner is right, a basic tenet of Mendelian genetics would be overthrown.
The critique of Skinner's results is led by L. Earl Gray, a U.S. EPA
toxicologist who has long studied vinclozolin's and methoxychlor's
disruptive effects on reproductive hormones.
"What he's doing doesn't have any real obvious implications for the risk
assessments on the chemical and has uncertain relevance to human or animal
health," Gray says. "And since [his results] can't be replicated, I'm not
sure they even demonstrate basic science principles."
Naturally, this sort of scathing criticism sits poorly with Skinner, who
responds, "If you're a toxicologist at the EPA, [the epigenetic paradigm
shift] scares you because it changes how you do toxicology." Although he
acknowledges that his findings could throw the reasoning behind chemical
regulation and the testing protocols used to determine chemical toxicity
into disarray, Skinner says this isn't what his studies were designed to do=
.
His team, he says, is simply using vinclozolin to induce a change in an
organism and studying the molecular mechanisms involved in that change.
Studies by scientists at BASF, the manufacturer of vinclozolin, and
Sumitomo, the manufacturer of methoxychlor, have not confirmed the
fourth-generation effects. Both company studies differed somewhat from
Skinner's in the mode of exposure, the subspecies of rat used and the
prenatal phase in which the dose was administered. Skinner believes all
these factors may explain why his results were not replicated =97 and
considers the BASF study to be "very appropriate for a risk assessment
study" that does not conflict with his results.
He also believes the challenges to his work represent "industry pushback"
similar to that experienced by researchers who have found harmful effects o=
f
other profitable chemicals such as bisphenol A, phthalates and atrazine.
At a July meeting of epigenetics experts sponsored by the National Academy
of Sciences, Gray called attention to an apparent case of scientific fraud
perpetrated by Hung-Shu Chang, one of Skinner's postdoctoral students, in
which much of the supporting data for a now-retracted 2006
*Endocrinology*paper was fabricated. In a prepared statement dated
September 2009, Skinner
notes that Chang worked only on this paper, and that there are nine other
peer-reviewed and published papers from his lab on the subject. The
scientific community has viewed the episode as an isolated incident that
does not taint the rest of Skinner's work, according to a Sept. 23 article
by Rebecca Renner in *Environmental Science & Technology*.
There is one thing Skinner and Gray agree on: More research is needed. In
his prepared statement, Skinner said the current conflict is "not
unexpected. My hope is as this research develops we maintain a scientific
objectivity and professionalism. ..." Skinner has two more papers in
preparation that he says will "calm things down" because they show the same
results in a mouse study as he found in his rat studies.
"We just need to be careful about our science," Gray says. "It sorts itself
out over time, and I think that's what this will do."
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