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Scientists Say They Can't Replicate Pioneering Epigenetic Results

The murky waters of the debate over chemical exposures and health just got murkier. And a bit nastier.

Last year, Miller-McCunereported on the striking research of Washington State University researcher Michael Skinner, who found that exposing rats prenatally to a widely used fungicide resulted in male reproductive malformations and malfunctions for four generations. Skinner believes the transgenerational nature of the effects occurred via epigenetic changes in gene expression during gestation — that is, the genes themselves weren't changed, but altered chemistry of the DNA scaffolding made the changes heritable.

Now Skinner's breakthrough 2005 study is being challenged by industry and government scientists who say it isn't replicable. If a study can't be replicated, scientific ethics require questioning its validity. A corollary to that principle is that if you can't nullify a scientific result by other means, attack the methodology used to arrive at that result.

Skinner and his team have carried out a series of experiments exposing pregnant Sprague-Dawley rats to high doses of vinclozolin, a fungicide used on a variety of agricultural products.

The transgenerational aspect of the damage is the really staggering feature of Skinner's research, because of its profound implications for human health, not to mention commerce. If damage to one generation carries on indefinitely into future generations, even when ensuing generations are not directly exposed, shouldn't we make our chemicals regulation policy far more rigorous immediately?

The question of industrial chemicals' influence on human health is decades old, and there is significant evidence that many of them — DDT, PCBs, bisphenol A, hexavalent chromium, to name a few — can disrupt the human endocrine system as well as cause cancer and other diseases. So it would be no surprise if vinclozolin turned out to be a similar bad actor.

But the prospect of multigenerational effects is "a new paradigm that changes everything," according to Jerry Heindel, a National Institute of Environmental Health Sciences program administrator. Heindel's statement appeared in a Sept. 23 article by Rebecca Renner in Environmental Science & Technology.

Two of the studies that tried to replicate Skinner's work were conducted by researchers working for corporations that manufacture and sell agricultural chemicals — the German giant BASF Corporation, which manufactures vinclozolin, and Japan's Sumitomo Chemical, which also produces a number of fungicides. While the relationship between the researchers and their employers is not necessarily a fatal conflict of interest, it can't be entirely dismissed. Some academic and EPA scientists have also been skeptical of Skinner's claims based on their own work.

The current state of play focuses on methodology. Skinner injected the fungicide directly into the abdomens of Sprague-Dawley rats, whereas other researchers have dosed rats orally. Not all the studies have used the Sprague-Dawley rat strain, and the EPA and BASF studies dosed the rats at different gestational stages. Only the Sumitomo experiment tried to replicate every aspect of Skinner's work. Skinner believes the strain of rat, as well as the breeding protocol, are factors in the disparate results, according to Renner's ES&T article.

The studies failing to show a transgenerational effect nevertheless demonstrate evidence of reproductive abnormalities caused by vinclozolin — which keeps the fungicide on the hook, so to speak. Endocrine disruption during gestation continues to be a worrisome and active focus of research.

Science is supposed to be self-correcting by just the sort of back-and-forth challenges that Skinner and his critics are engaged in. The stakes are extremely high for human health, the environment, and economic interests. I hope the outcome is decided by further creative and clarifying research — not by financial concerns.

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