Surely you've heard about BPA by now. It's everywhere. Some 7 billion pounds of it were produced in 2007. It's in adhesives, dental fillings, and the linings of food and drink cans. It's a building block for polycarbonate, a near-shatterproof plastic used in cell phones, computers, eyeglasses, drinking bottles, medical devices, and CDs and DVDs. It's also in infant-formula cans and many clear plastic baby bottles. Studies have shown that it can leach into food and drink, especially when containers are heated or damaged. More than 90% of Americans have some in their bodies.
BPA is dangerous to human health. Or it is not. That's according to two government reports in recent months that came to opposite conclusions. The National Toxicology Program (NTP), which is part of the National Institutes of Health, reported in September 2008 "some concern" that BPA harms the human brain and reproductive system, especially in babies and fetuses. Yet less than a month earlier, the U.S. Food and Drug Administration declared that "at current levels of exposure" BPA is safe. Even after the FDA's own science board questioned the rigor of this analysis in late October, the agency didn't change its position.
Let's take a moment to ponder this absurd dichotomy. How could our nation's health watchdogs reach such divergent conclusions? Are we being unnecessarily scared by the NTP? Or could the FDA be sugarcoating things? What exactly is going on?
We went on a journey to find out. What we learned was shocking. To some degree, the BPA controversy is a story about a scientific dispute. But even more, it's about a battle to protect a multibillion-dollar market from regulation. In the United States, industrial chemicals are presumed safe until proven otherwise. As a result, the vast majority of the 80,000 chemicals registered to be used in products have never undergone a government safety review. Companies are left largely to police themselves.
Just five companies make BPA in the United States: Bayer, Dow, Hexion Specialty Chemicals, SABIC Innovative Plastics (formerly GE Plastics), and Sunoco. Together, they bring in more than $6 billion a year from the compound. Each of them referred questions about BPA's safety to their Arlington, Virginia -- based trade association, the American Chemistry Council. "Our view would be, Well, no, there isn't anything to be concerned about," says Steve Hentges, the council's point person on BPA. "In a sense, you could have 'some concern' about just about anything."
Perhaps. But consider this: Of the more than 100 independently funded experiments on BPA, about 90% have found evidence of adverse health effects at levels similar to human exposure. On the other hand, every single industry-funded study ever conducted -- 14 in all -- has found no such effects.
Of the more than 100 independently funded experiments on BPA, about 90% have found evidence of adverse health effects. On the other hand, every single industry-funded study ever conducted -- 14 in all -- has found no such effects.
It is the industry-funded studies that have held sway among regulators. This is thanks largely to a small group of "product defense" consultants -- also funded by the chemical industry -- who have worked to sow doubt about negative effects of BPA by using a playbook that borrows from the wars over tobacco, asbestos, and other public-health controversies. A secretive Beltway public-relations consultant. A government contractor funded by the industries it was hired to assess. A Harvard research center with a history of conflicts of interest. These have been the key actors in how the science of BPA has been interpreted by the government. And it is their work, as much as the science itself, that has stymied regulation.
There are a few facts about BPA that everyone agrees on. One is that people are constantly exposed to the compound. Babies -- particularly those fed canned formula via polycarbonate bottles -- are at the highest risk from BPA; their undeveloped digestive systems metabolize it poorly. It's also undisputed that BPA mimics the female sex hormone estrogen, and that some synthetic estrogens can cause infertility and cancer.
What is in dispute is whether the tiny doses of BPA we're exposed to are enough to trigger such hormonal effects. For decades, the assumption was that they didn't. This was based on traditional toxicology, which holds that "the dose makes the poison." In other words, a threshold exists below which a compound is harmless. This makes intuitive sense. Consider alcohol: The more you drink, the drunker you get; but if you drink just a little -- below the threshold -- you may not feel anything. In the 1970s and 1980s, government scientists used standard toxicology to test BPA. They concluded that, at doses far higher than those found in humans, it may cause organ failure, leukemia, and severe weight loss. Yet as BPA products have made their way into every part of our lives, biologists have discovered evidence that very low doses may have a completely different set of effects -- on the endocrine system, which influences human development, metabolism, and behavior.
At first, these discoveries emerged by accident, when test tubes and petri dishes in laboratories were switched from glass to plastic. A group of Stanford researchers in 1993 found that breast-cancer cells it was studying reacted with a mysterious estrogen, which it traced to polycarbonate lab flasks. A few years later, Patricia Hunt, a geneticist at Case Western Reserve University, discovered abnormalities in the chromosomes of her lab mice. She eventually concluded that damaged polycarbonate cages were at fault.
In 1995, a developmental biologist named Frederick vom Saal stepped into the picture. A tenured professor at the University of Missouri -- Columbia, with funding from the National Institutes of Health, vom Saal tested BPA to see how it interacted with samples of human blood. He found that, because it bypassed mechanisms that control the dose of hormones in the body, its estrogenic effects were magnified. "We said, 'Wow, that's bad. This stuff should be considered a lot more potent than it is,' " vom Saal recalls. He then fed small amounts of BPA -- 25,000 times lower than the EPA's toxic threshold -- to pregnant mice. He discovered that the compound enlarged the prostates of the male offspring, signaling potentially serious developmental disorders. His study was published in 1997 in the peer-reviewed journal Environmental Health Perspectives.
In the years since, more than 100 experiments have shown BPA to cause permanent harm in lab animals at the low exposure levels found in humans. In 2000, Chandra Gupta, a biologist at the University of Pittsburgh, replicated vom Saal's prostate study. Hunt, the geneticist, replicated under controlled conditions her findings of damage to mouse chromosomes. Others have found impacts on sperm production, testes development, and mammary-gland tissue, as well as behavioral disorders including hyperactivity, aggressiveness, and impaired learning. Most recently, scientists found a correlation (though it's impossible to determine causation) between BPA levels and heart disease and diabetes in humans.
If these low-dose findings were counterintuitive to toxicologists, they made perfect sense to developmental biologists. After all, BPA is a synthetic hormone. Any physician knows that at small doses, most hormones are extremely powerful in stimulating their target organs, while at higher doses -- above a certain threshold -- they can paralyze these same organs. (Testosterone powers the male sex drive, for instance, but at high doses causes impotence.)
What's more, BPA is hardly the only chemical to be identified as an "endocrine disrupter." To date, more than 50 such compounds have been identified. Dioxins, PCBs, and DDT are some of the more infamous examples. Some cosmetics and soft plastic toys contain one or more phthalates -- a group of chemicals that interfere with testosterone and have been shown to lead to infertility and cancer. But because BPA is used in so many common products and has shown effects at such low doses, Hunt says, it quickly became the "poster-child chemical for these endocrine disrupters."
Rats in the Lab
As the evidence against BPA has mounted, some 29 studies have found the opposite: that the compound is safe. While these experiments have been fewer in number, many of them have the advantage of being far larger in sample size -- and thus, their backers say, more statistically significant. Yet the largest of these studies also have another thing in common: They have been funded by BPA's manufacturers. Sample size, of course, isn't the only criterion for judging a study. There's also methodology, lab procedures, and interpretation of data. And a close look at the big industry-funded studies indicates significant flaws.
One of the first such studies, paid for by the trade group Society of the Plastics Industry, was directed by Stuart Cagen of Shell Chemical Co.; another was conducted by John Ashby, at the AstraZeneca lab in the U.K. Both were attempts to replicate vom Saal's experiment. Published in 1999, the Cagen and Ashby studies gave BPA a clean bill of health. Independent scientists, though, questioned the findings. In addition to testing BPA, Cagen and Ashby had tested the chemical DES as a "positive control" -- a lab procedure to determine if a study is conducted properly. Although DES is known to harm mice, neither study found any effects from it. By the definition of a positive control, this indicates the experiments were flawed. (Cagen declined comment; Ashby has retired and could not be reached.)
The largest and most influential industry studies have been conducted by Rochelle Tyl of the Research Triangle Institute, a private lab in North Carolina. Tyl's first BPA study, published in 2002 at a cost that Tyl puts at around $2 million (also funded by the Society of the Plastics Industry), examined three generations of rats and found no adverse effects at low doses. Yet here, too, there are questions of protocol. The study used a rat strain called the CD Sprague-Dawley, which has been shown to be insensitive to synthetic estrogens like BPA. (A Japanese study found that the CD Sprague-Dawley rat can withstand a dose of synthetic estrogen more than 100 times greater than what a female human can tolerate.) As of early 2007, of the 29 studies that have shown no harm due to BPA, 13 have used the CD Sprague-Dawley rat. Nonetheless, when the FDA declared BPA "safe" this fall, it relied almost exclusively on Tyl's work -- a shortcoming that the agency's science board publicly criticized in October.
To address criticisms of her first study, Tyl recently completed a follow-up, this time with funding from the American Chemistry Council. "It doesn't matter who pays for my studies," says Tyl, who denies there has been any industry influence over her experiments. "It offends the living bejesus out of me, that I'm going to alter a study design or a result." The follow-up used mice instead of the CD Sprague-Dawley rat and also found no adverse effects from low-dose BPA. However, the study's details indicate that the mice were fed a type of animal chow that has been shown to mask the effects of estrogens like BPA. Moreover, according to Tyl's own data, the prostates in both her experimental and her control mice were enormous, suggesting that her study had, in fact, shown effects from BPA, or that there were significant flaws in her team's lab practices.
Harvard to the Rescue
With two pools of warring studies, BPA regulation has hinged on scientific reviews that assess and pass judgment on the overall body of research. In April 2001, a select group of scientists received a letter emblazoned with the Harvard University crest inviting them to sit on the first such BPA panel. The Harvard Center for Risk Analysis (HCRA), a program under the Harvard School of Public Health, would assume "much of the technical writing responsibilities," the letter explained. In exchange for attending three two-day meetings and reviewing drafts of the panel's report, the scientists would be paid $12,000 apiece plus expenses. The letter noted that the Society of the Plastics Industry had commissioned the study and that the panel's deliberations would be private. The letter concluded, "I assure you it will be a stimulating and productive experience."
"I said, 'Great! This is a Harvard center. They're obviously an honorable bunch,' " recalls one accomplished biologist on the panel, who spoke on condition of anonymity. What he didn't know at the time, he says, was that the center has a history of conflicts of interest. Under founder John D. Graham, a Harvard professor and later administrator of the Office of Information and Regulatory Affairs in the George W. Bush White House, the center had solicited funding from companies whose business might be affected by its research. HCRA's donors have included more than 100 corporations, including BPA producers Dow, Shell, and Germany-based BASF, as well as industry associations such as the American Chemistry Council.
"In the past, HCRA has acted very much like a product-defense group," says David Michaels, a Clinton-era Energy Department official and author of the book Doubt Is Their Product. "In a 2000 study, paid for by AT&T Wireless, HCRA justified letting motorists talk on their cell phones by arguing that the added productivity outweighs the cost of accidents. Three years later, in a Harvard-funded study, the same researchers found that not to be true." A more recent example: In 2005, the center published a study concluding that "government advisories on fish consumption and mercury may do more harm than good"; the lead researcher didn't disclose that most of the study's $500,000 in funding was underwritten by the United States Tuna Foundation.
Back in October 1991, in a letter to Philip Morris (obtained through the archives of tobacco-industry files released during litigation and maintained by the University of California, San Francisco), Graham demonstrated how HCRA could recast opposition to regulation as concern for the greater good. In the D.C. debate on fuel-efficiency standards, he noted, "We have urged consideration of the safety risks associated with smaller vehicles." The letter concluded with an appeal for money and an offer of assistance. In an internal memo, a Philip Morris executive noted, "Depending on the 'vibes' you guys get when you meet Graham, I would also be in favor of PM becoming a contributor to the center."
When it came to its BPA review, the Harvard center held several meetings of its panel between summer 2001 and 2002. But then the report languished for two years, during which time dozens of studies were released that strengthened the case against BPA, including a human study that linked the compound to ovarian cysts (a cause of infertility). None of those findings made it into the final report. Instead, the review, published in the journal Human and Ecological Risk Assessment in 2004, focused on Tyl's research and a few other industry studies that downplayed BPA's health concerns. The review concluded that there is "no consistent affirmative evidence of low-dose BPA effects."
Several members of the 12-person panel didn't feel comfortable with the conclusions. Four removed their names from the study. One of those scientists, Marvin Meistrich, says, "I disagreed with the way the final report was prepared." After the panel's last meeting, the Harvard center selected additional studies to include in its review -- "ones that tended to demonstrate no effects," says Meistrich. One panel member who did sign the report, Claude Hughes, turned around and less than a year later published a paper with vom Saal in Environmental Health Perspectives (the NIH's premier journal) that refuted the Harvard center's conclusions.
In the end, HCRA paid even the scientists who pulled their names from the review. The published paper's acknowledgments thank them by name for their "helpful comments and guidance." That, in itself, is a score for BPA's defenders: These scientists have rare specialties that would be vitally important if BPA were to wind up in court. A judge could rule that they had a conflict of interest. "It's fairly commonplace for companies facing tort suits to corner the market on experts, making it more difficult for the plaintiff to hire witnesses," says Peter Nordberg, a toxic-tort lawyer at Berger & Montague in Philadelphia.
Through a spokesperson, George Gray, the acting director of the Harvard center at the time, declined to comment on the study. (Shortly after the HCRA review appeared, President George W. Bush appointed him assistant administrator of the EPA.) For its part, the Harvard School of Public Health distances itself from the center's controversial past. "HCRA is a much different place since John Graham left [in 2001]," says assistant dean Robin Herman. Graham says that industry-funded studies at the center have always been subject to "rigorous quality-control procedures."
You might expect that a compromised review like this would wither away. Yet the opposite is true. The plastics industry still uses it as evidence that BPA is safe. Journalists and consumers who visit bisphenol-a.org, a site created by the American Chemistry Council, can see that none other than Harvard University has weighed in and pronounced BPA harmless.
Read the rest of this article at Fast Company By David Case Fast Company January 14 2009