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In 1999, Guillette began collaborating with Taisen Iguchi of Japan's Okazaki National Research Institutes to sequence hundreds of alligator genes related to reproduction, particularly those related to estrogen receptors. "This allowed us to start talking about the genetic basis of the alligator, which not only gave us a powerful tool box for understanding alligators but also for doing comparisons with mice and humans. The genetic mechanisms that turn reproductive development on and off are almost identical whether you're studying a mouse, a human, or an alligator."
The researchers also learned that even trace amounts of hormonal imposters could have an impact. "Hormones work at incredibly small concentrations," says Guillette.
While he is careful not to draw parallels between alligators and humans, Guillette says it would be naïve to dismiss the implications, considering that reproductive hormones in both species are very similar. In fact, the similarities are so great that, in 2006, the National Institute of Environmental Health Sciences (NIEHS) awarded a grant to Guillette to study ovarian development in alligators.
"At NIEHS we are not interested in alligator health, but Lou shows how understanding that can inform studies on animal models and humans," says Jerry Heindel, scientific program administrator for the NIEHS Cellular, Organ and Systems Pathobiology Branch. "That is why we fund him. He sees the big picture and helps people connect the dots."

Although the alligator is important as an animal model for human disease, Guillette is also interested in alligator health per se. And he is committed to protecting the species.
"I want to conserve and preserve these animals and the environment they live in," Guillette says. "Alligators are a charismatic species that people care about. Plus, if you know that alligators are having problems in the lake, you can assume that all the other species there, many of which people really don't care about, are also having problems."
He points out that, because of the alligator's high profile, Florida and the federal government have purchased thousands of acres of farmland around Lake Okeechobee, a massive lake in south-central Florida where Guillette also found alligator reproductive problems, and are restoring it to a wild state. Preserving alligator habitat is also a core goal of the federally funded Everglades restoration project.
Guillette acknowledges that some may wonder why all the effort. "I've heard people say we're up to our armpits in alligators, but what we're really up to our armpits in is people," he says. "It's not that there are so many alligators. It's just that people are pushing them into smaller and smaller spaces."

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