Air Date: Week of August 1, 1997
Just over a year ago, a research team at Tulane University in new Orleans published some startling results. The group reported that pesticides were hundreds of times more toxic in pairs than one at a time. Such synergistic effects had been reported before, but the staggering magnitude reported caught researchers around the world by surprise. Then last month Professor McLachlin withdrew the study, saying he could not replicate the results. Steve talks with Living on Earth's Dan Grossman about what happened.
CURWOOD: This is Living on Earth. I'm Steve Curwood. Just over a year ago, a research team at Tulane University, in New Orleans, published some startling results in the journal Science. The group, based in the laboratory of endocrinologist John McLachlan, reported that pesticides were hundreds of times more toxic to cells when tested in pairs, that at one at a time. Such synergistic effects have been reported before, but the staggering magnitude caught researchers around the world by surprise. Then, last month, Professor McLachlan surprised the world again, this time by retracting the study, saying he could not replicate the results. Living on Earth's Daniel Grossman has our report.
GROSSMAN: John McLachlan and his team at Tulane University, were trying to put to rest a puzzle bedeviling environmental scientists. It's believed some pesticides and plastics that mimic estrogen and other hormones, have a number of effects. Among other things, they've been linked to lower sperm counts, and reproductive cancers in humans; and altered sexual development in wildlife. But in the laboratory, these chemicals seem too weak to be the culprits. But Tulane researchers thought maybe combinations of the substances would be more potent. Chemicals are usually tested for toxicity one at a time, even though humans and animals encounter them in complex arrangements. But previous studies of fish cells, turtle eggs, and human breast cells, demonstrated that the effects of these chemicals, are magnified in mixtures, up to 10-fold. McLachlan's experiment used a yeast cell, modified with human genes, and it found an apparently whopping synergistic effect. Four pesticides, tested in pairs, seemed to be up to 1600 times more potent than would be expected if the effects of two were simply added together. The discovery attracted the attention of Federal regulators scrambling to figure out how to screen chemicals, for their ability to disrupt the endocrine system. Such gigantic synergistic effects could vastly complicate their task. The research also caught the eye of many scientists, who set out to replicate the surprising results. At least five research teams joined the fray. And so far, they've all come up empty-handed. Donald McDonnell is a pharmacologist at Duke University.
MCDONNELL: What we were able to show was, if these compounds were very, very weak estrogens, these compounds that McLachlan had tested, and when tested together, their activity's no more than additive, and not the synergistic. And so there was no surprises.
GROSSMAN: Meanwhile, McLachlan himself discovered he couldn't repeat the experiment, so last month, he published a letter in "Science," retracting his original findings. His letter left a lot of researchers scratching their heads, wondering how such a mistake could occur in the lab of a respected scientist like John McLachlan, who formerly directed a federal research program. Some scientists wonder if some contaminant fouled up the original experiment. Others speculate that maybe the synergy effect really did occur, but some critical factor that no one knows about, changed in the laboratory. The big question is, what to do next. Some researchers now dismiss synergy as an important effect, and say the traditional, one at a time method of testing compounds, is vindicated. But others, like Tufts University biologist Ana Soto, disagree. Professor Soto herself has found that certain synthetic chemicals affect human breast cells 10 times more powerfully in mixtures.
SOTO: This hasn't changed anything, the fact that the paper was retracted. There are several other publications that show more than additive effects. They are not 1000 times higher than expected from simply additive, but they are none the less synergistic.
GROSSMAN: Meanwhile, Dr. Malathy Shekar of Wayne State University is reporting that she's seen large synergistic effects, more than 100-fold, in her experiments on breast cells. But her research hasn't been published yet, so it's a little too early to give it much weight. For Living on Earth, I'm Daniel Grossman.
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