Missouri biologist Frederick vom Saal and his team exposed the dangers of bisphenol A — and earned the wrath of the plastic industry.

Vom Saal is speaking from his office at MU's Lefevre Hall, a two-story, white-stone building where biology classes are held, including vom Saal's popular graduate class on mammal­ian reproduction. Several framed photographs of vom Saal's wife, their daughter and his single-engine Cessna 210 (he's a pilot) sit atop file cabinets, but the rest of the office is dominated by shelves of document-stuffed accordion folders and thick academic texts.

Soon, he's joined by Wade Welshons, a professor of biomedical sciences, and Susan Nagel, a professor of obstetrics, gynecology and women's health. They are two of vom Saal's research partners who, along with four other professors, make up the Endocrine Disruptors Group. It's a new field of study that vom Saal, Welshons and Nagel helped establish.

Nagel has a cheerful voice and an infectious laugh; she pulls up a chair in vom Saal's office. She came to vom Saal's lab as a grad student in 1993, working with breast-cancer cells. Not long after vom Saal had made his first observations using bisphenol A, he suggested to Nagel that she take up the work.

Nagel recalls, "He said, 'I have this project that's just guaranteed to be a short study, and you'll get a publication out of it. You already know how to do the techniques, so all you have to do is go over to his [Welshon's] lab and just turn this out.'"

The "short study" ended up taking her more than two years, but Nagel did come out of it with a publication — a landmark. Toxicologists' tests on bisphenol A claimed that it was nontoxic at extremely high doses, but Nagel's study showed that bisphenol A was hormonally "active" — meaning it caused an effect — in cells at levels thousands of times lower than toxicologists had previously deemed to be safe.

These "low-level effects," as Nagel's findings came to be called, represented a whole new way of thinking about chemicals and human safety. Toxicologists look at high doses of chemicals to find out how much is necessary to cause serious harm — birth defects or death. But endocrinologists know that the amounts of a substance necessary to cause harm on a hormonal level are tiny and can pack profound consequences. Exposing a developing fetus to additional estrogen, for example, can permanently alter crucial phases of development, irreversibly altering systems that are designed to react to the most miniscule changes in hormone levels.

To his students, Welshons explains low-dose hormonal effects this way: A cubic millimeter of a chemical is a milligram, which is a relatively large amount. If you take one thousandth of that, you have a microgram, which is visible to someone with excellent eyesight. (It's the smallest particle a human eye can resolve.) If you take one of those microgram particles, waft it onto the floor, step on it and grind it into a thousand more particles, you have nanogram particles, which are invisible to the naked eye. If one of those nanogram particles floats into the air and lands in a 1-liter container of liquid and dissolves there, it creates a solution that, in the case of bisphenol A, will stimulate human breast-cancer cells in a cell culture, causing the cancer cells to proliferate.

Nagel's first study showed that low doses of bisphenol A could have effects; further research indicated that bisphenol A enlarged the prostates of laboratory mice. She demonstrated that the effects in mice occurred at doses close to what humans are exposed to each day from sources such as food packaging. Her study was published in the January 1997 issue of Environmental Health Perspectives, a journal put out by the National Institutes of Health.

A second publication of Nagel's findings — this time noting that bisphenol A lowered sperm counts in mice — was approaching when, in late 1997, vom Saal received a visit from John Waechter, a scientist with Dow Chemical. Waechter introduced himself as a representative of a group then called the Chemical Manufacturers Association.

The meeting took place in a conference room in the biology department. Vom Saal and Welshons were there, as were the chairman of MU's biology department and a visiting professor from the University of Illinois. Welshons remembers that Waechter seemed nervous during the meeting.

"He gave all the signs of feeling like he'd been asked to do something which was wrong," Welshons says.

Waechter told the group that the Chemical Manufacturers Association was surprised at the findings in vom Saal's lab and that the association wanted to try to replicate the bisphenol A findings in a larger, industry-funded study.

"They offered a very large, very expensive study," Welshons says. "Obviously a lot of money to the University of Missouri, that's what those things mean. Not money for us personally but as research support."

Vom Saal says he'll never forget Waechter's words: "Can we arrive at a mutually beneficial outcome where you withhold publishing this paper until authorized to do so by the Chemical Manufacturers Association?"

The scientists felt they were being offered a bribe.