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The Frog of War

When biologist Tyrone Hayes discovered that a top-selling herbicide messes with sex hormones, its manufacturer went into battle mode. Thus began one of the weirdest feuds in the history of science.

Tyrone Hayes confronts one of his research subjects at his UC-Berkeley laboratory.: Annie TrittTyrone Hayes confronts one of his research subjects at his UC-Berkeley laboratory. Annie TrittAtrazine has long been a mainstay of American agriculture. Registered for use in 1959, it is now used on half the nation's corn and 90 percent of our sugarcane, not to mention lawns, golf courses, and Christmas tree farms. All told, about 80 million pounds of it are applied each year, making it the most widely used herbicide after glyphosate, a.k.a. Roundup. While Syngenta, the largest producer, won't disclose its profits from atrazine, the company earned $2.3 billion in 2010 from its line of selective herbicides (those that only kill specific plants), of which atrazine is the leading product. Sales keep rising as more weeds develop resistance to Roundup: Syngenta reported a 14 percent bump in the first half of 2011.

In 1997, EcoRisk approached Hayes on behalf of Syngenta's corporate predecessor, Novartis. They wanted him to study atrazine, which at the time was going through a product reapproval process mandated by the EPA. Hayes took the gig, figuring Novartis wouldn't ask him to look into the herbicide's effects if it expected him to find anything. "My hypothesis was, nothing's going to happen," he recalls.

Yet something did. In his experiments, male Xenopus exposed to atrazine had shrunken voice boxes, which put them at a disadvantage for courting females. That was startling enough. But when Hayes examined the frogs' gonads, he discovered something more disturbing: About a third of the exposed males had malformed reproductive organs. Many were hermaphrodites, with both ovaries and testes. Some had more than two of each organ—and some of the testes produced eggs instead of sperm.

Xenopus are not naturally hermaphroditic, and no intersex frogs were found in Hayes' control tanks. But gender deformities were present among frogs exposed to as little as 0.1 part per billion (picture a thousandth of a grain of salt in a half gallon of water). That's 30 times less than the 3 ppb the EPA allows in our drinking water.

Since 1980, scientists had been reporting shrinking amphibian populations—close to one-third of known species are now in danger of extinction. Hayes was intrigued to think he might have discovered a cause for the decline. "Everybody is out there looking for dead frogs and what killed the frogs," he explains. "We're asking, 'How come there aren't any new frogs?' Atrazine isn't killing the frogs. But if they're reproductively impaired, that's killing the population."

To Hayes' surprise, EcoRisk and Novartis didn't seem as concerned about his findings as he was. He was asked to repeat the studies but wasn't given the necessary funding, he says, and EcoRisk scientists suggested statistical manipulations that made the voice box effect appear to vanish. Hayes weighed simply handing over his data. After all, this was contract work. "It's just like if I was an artist and you told me to paint you this color, and I paint you that color and you buy the painting and I'm done with it," he says.

Despite Syngenta's claims to the contrary, atrazine's feminizing effects are documented in dozens of  peer-reviewed, reputable studies.

In the end, he couldn't do it. In 2000, he resigned from the panel of scientists working for EcoRisk. He then repeated the experiment, twice, and in April 2002 published his findings in the Proceedings of the National Academy of Sciences. He has since published a dozen atrazine papers in peer-reviewed journals and replicated his findings with two other frog species, both in the lab and in nature. One study, published in pnas in 2010, found that when 40 male Xenopus hatched in water contaminated with atrazine at a level of 2.5 ppb, three-quarters wound up chemically castrated or partially feminized; four, like Darnell, changed genders completely. He has also tracked a population of leopard frogs in a Wyoming pond for a decade, documenting how the ratio of males to females rises and falls in tandem with atrazine levels.

Hayes postulates that atrazine affects gender by activating a gene that produces an enzyme called aromatase, which converts androgens—male sex hormones—to estrogens. In his talks, he makes sure to point out that estrogen is the same in frogs and humans. Just like frogs, we begin our development steeped in an aqueous environment: amniotic fluid. The chemical that so powerfully alters the gonads of a frog may be having an effect on us, too.

As assiduously as Hayes researches links between atrazine and hermaphroditic frogs, Syngenta attempts to disprove them, funding a stream of research that has found, variously, that atrazine exposure did not produce intersex frogs, that intersex frogs can be found regardless of atrazine exposure, and that atrazine exposure produces intersex frogs only at very high concentrations. "No reliable, replicable studies have ever linked atrazine to effects on frog sexual development," Syngenta spokeswoman Ann Bryan told me via email, noting that previous EPA reviews have determined that "atrazine does not adversely affect amphibian gonadal development." (Syngenta officials declined to be interviewed but agreed to answer a few written questions.)

Actually, atrazine's unintended effects are documented in dozens of peer-reviewed studies. Last year, Jason Rohr and Krista McCoy from the University of South Florida published a meta-analysis of research involving amphibians and fish and found consistent results indicating that the herbicide affects the reproductive and immune systems. This past year, Hayes gathered 21 coauthors for a paper in the Journal of Steroid Biochemistry and Molecular Biology showing that atrazine disrupts normal hormonal function, with demasculinizing effects on male gonads in reptiles, fish, amphibians, and mammals. He and 40 coauthors from 13 countries will soon publish a literature review that reaches similar conclusions. "I'll have every scientist, with a few exceptions, who has worked on atrazine saying, 'We're together,'" he promises.

Perhaps if Syngenta had simply questioned Hayes' research in academic journals, things might have stayed focused on questions of sample sizes, lab conditions, and so on. But the company began sending staff to Hayes' research talks in the United States and abroad, where he says they sometimes passed out materials disparaging his methods and accusing him of fabricating results or refusing to share data. "A Syngenta representative does try to attend events where Dr. Hayes is speaking," Syngenta's spokeswoman confirmed. "It's in our best interest, and farmers', that we have the opportunity to counter his outrageous accusations."

After a Syngenta scientist argued that atrazine was a vital tool for US farmers, Hayes responded in an email, "I've got your vital tool right here."

Over time, these tense interactions escalated into the kind of verbal jostling you'd expect in a high school hallway. Syngenta officials, according to Hayes, have made derogatory remarks about his appearance, his speaking style, and even his sexual proclivities, which sounds implausible until you consider that Syngenta's PR firm, Jayne Thompson & Associates, once proposed a covert media campaign to discredit the court system in an Illinois county where judges are presiding over an atrazine lawsuit.

At one conference in 2005, he contends, Syngenta staff scientist Tim Pastoor accused him of "cherry-picking data" and asked if he cherry-picked his dates as well. Hayes responded in an email: "don't worry...daddy has no intentions of picking your cherry." At another meeting, Pastoor asserted that atrazine was a vital tool for US farmers. Hayes emailed him to ask, "How long have YOU been a 'vital tool'?" adding, "I've got your vital tool right here."

While there was a certain frat boy humor to this scientific smack talk, there was also an element of psychological warfare. After Hayes gave a lecture at the Society of Environmental Toxicology and Chemistry confab in 2007, he received an email from Syngenta scientist Alan Hosmer, whom he knew from his EcoRisk days: "You lost and everyone at SETAC was calling you an entertaining fraud," Hosmer wrote.

Hayes felt the message was designed to arouse a black academic's worst anxieties: the fear of being seen as a buffoon or an affirmative-action mistake. This time, Syngenta reps received a six-page email response titled: "I OWN THIS: A MADMAN'S MANIFESTO." In it, Hayes bragged of his fame ("I get paid $10,000 for talking for an hour"), ridiculed Syngenta's research ("nothing you have done can touch the quality of my work"), and waxed poetic about how his kids attend the fancy "white private schools" that were unavailable to him. He also deployed his favorite phrase—"I don't give a fuck"—shortened to an acronym: "IDGAF! Come on?????...do you think I care about propriety and professionalism?...I have used the 'F-word' in my talks, have quoted DMX, Busta Rhymes, Tyra Banks, Marvin Gaye...I pack the room, have em' call out security...and have been invited back every year. That's my house, Trick!"

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