STATS ARTICLES 2010
Minority Report: Did the Presidentís Cancer Panel Abandon Science for Scientific Politics?
Trevor Butterworth, May 13, 2010
Unflattering reviews from cancer experts as the panelís failure to invite experts from the Food and Drug Administration, Environmental Protection Agency, the National Academy of Sciences, the National Toxicology Program and the Occupational Safety and Health Administration to comment on environmental chemical risk has undermined the reportís scientific accuracy and credibility.
Last week, the President’s Cancer Panel issued a report which seemed to confirm environmental activists’ worst nightmare: the proportion of cancer cases caused by exposure to chemicals in the environment has been “grossly underestimated,” it said, noting that these chemicals were capable of causing “grievous harm.”
But after the initial shock, there was a “hold-on-a-minute” moment, as experts – notably the American Cancer Society – digested the findings. As Reuters and other news organizations began to note:
The criticism made two inter-related points: the panel was one-sided in its presentation of the science of evaluating the risks from chemicals in the environment and thus grossly exaggerated the impact of these chemicals on cancer (the American Cancer Society estimates between 4 and 6 percent of cancers may have an environmental chemical trigger); as a consequence, the claim that these kinds of cancer have been “grossly underestimated” distracts the public from focusing on the major and preventable causes of cancer – particularly smoking.
The President’s Cancer Panel looked at four different environmental sources of cancer in a series of four panel meetings held in 2008 and 2009. A close examination of the minutes of the meeting on chemical exposures and how that meeting shaped the final report reveals some surprising information that raises troubling questions about the role of the panel, and its commitment to scientific accuracy.
The meeting examining chemical risks from industrial and manufacturing processes took place in East Brunswick, New Jersey on September 16, 2008. Even as the summary of the meeting noted that the government “agencies responsible for both assessing risk and regulating occupational and environmental carcinogens include the Environmental Protection Agency (EPA), the (OSHA), and the Food and Drug Administration (FDA),” along with the National Toxicology Program (NTP), the International Agency on Cancer Research (IARC), and the U.S. National Academy of Sciences, there were no representatives from any of these agencies at the meeting.
Instead, the panels were composed of long-time critics of the way these agencies regulate chemicals.
One specific problem that results from this is shown in the testimony by Devra Davis, Director of the Center for Environmental Oncology at the University of Pittsburgh Cancer Institute. She is also the author of a controversial book, The Secret History of the War on Cancer, which was criticized in New York Review of Books’ review, Malignant Maneuvers, by the editor-in-chief of the Lancet, Richard Horton and in the Lancet by the Director of the International Agency for Cancer Research, Peter Boyle. Boyle observed that
“Devotees of conspiracy theories and aficionados of gossip and innuendo will be drawn towards this book like wasps to a juicy piece of meat… highly selective… A general theme that runs through the book is that it seems to be somewhat acceptable in Davis's eyes to consult for the tobacco industry, whereas anyone who consults for the chemical industry is a nasty person taking part in an enormous cover up… With so many important factual inconsistencies in dealing with areas with which I have some familiarity, I start to have concerns about the factual accuracy in the areas I do not know so well.”
(The book, by contrast, received a glowing review in Environmental Health Perspectives from James Huff, associate director for chemical carcinogenesis at the National Institute of Environmental Health Sciences; however, the review did not disclose that Huff and Davis are co-authors of multiple scientific papers.).
Dr. Davis raised the specter of BPA as a carcinogen at the meeting. As the summary of her presentation notes:
“The National Toxicology Program asserts there is cause for concern from exposure to bisphenol-A (BPA). BPA has been associated with prostate and breast cancers, obesity, miscarriages, brain disorders, and reproductive abnormalities, including feminization of males and masculinization of females. Interestingly, exposure to nutritional supplements (e.g., genistein, folates, Omega 3 fatty acids, vitamin D, calcium) prior to BPA exposure may negate its detrimental effects. However, the public should not have to guard themselves from a chemical that can be eliminated from the environment.”
But the National Toxicology Program did not “assert” this in 2008. The NTP report was not a quantitative risk assessment but a qualitative overview of the evidence at the time, expressed in five categories of “concern” in non-technical language and in order of worry: negligible concern, minimal concern, some concern, concern, and serious concern.
The NTP said that it had "negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. It said that there was negligible concern that exposure to bisphenol A causes reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. It said that there was some concern for neural and behavioral effects in fetuses, infants, and children at current human exposures and some concern for bisphenol A exposure in these populations based on effects in the prostate gland, mammary gland, and an earlier age for puberty in females.
As Michael D. Shelby, PhD, director of the National Toxicology Program's Center for the Evaluation of Risk to Human Reproduction cautioned WebMD, the evidence from rodent studies was "very limited:"
“Even in the areas where we've expressed some concern, the literature is not consistent on the endpoints reported. Some people find these effects; others may not, and their relevance to effects on human health -- there's still some uncertainty about that. That's why we didn't have a lower or higher level of concern in our conclusions."
A couple of months later the European Food Safety Authority – and several environmental and health agencies in European countries – dismissed the research that the NTP used to justify “some concern” as being poorly done. The Food and Drug Administration appeared to reach the same conclusion by the same route.
Again, if the panel had invited someone from the National Toxicology Program to comment on BPA, it would not have had to rely on hearsay about its report which ended up mischaracterizing its findings.
Nevertheless, two years is a long time in the controversy over BPA and the NTP brief has been superseded by significant research on including a study by the EPA, Ryan et al, which failed to find any evidence for neural and behavioral effects.
In summarizing the state of the evidence on BPA for a highlight in Toxicological Sciences, the world’s leading toxicology journal, Richard Sharpe, Chairman of the United Kingdom’s Expert Panel on Endocrine Disruption, and Principal Investigator at the Medical Research Council’s Reproductive Sciences Unit, wrote that -
Ryan et al also confirms previous findings “from studies involving large numbers of animals… conducted by recognized world expert groups,” wrote Sharpe (for more on this issue, click here).
When we move to the final report of the President’s panel, it would appear none of this research from recognized world expert groups exists. Despite the EPA taking the lead on trying to determine whether low doses of BPA such as might be ingested from consumer products can be shown to be harmful, neither of its key studies are mentioned or cited in the footnotes. There is, instead only evidence of danger, largely sourced to scientific research (vom Saal et al.) rejected by the FDA, EPA, EU, Japan, and Australia/New Zealand.
The report on BPA
In the opening letter to the President, the panel notes that:
“bisphenol A (BPA), is still found in many consumer products and remains unregulated in the United States, despite the growing link between BPA and several diseases, including various cancers.”
Later on the report says,
“Consumers have become increasingly anxious about the estrogenic effects of an organic compound, bisphenol A (BPA) that is used to harden plastics (e.g., baby and water bottles) and line the inside of food and beverage cans, including infant formula cans. BPA, which is detectable at biologically active levels in the urine of an estimated 93 percent of Americans, can leach into food when the plastic containers are heated in a microwave oven or washed in a dishwasher. Over the past decade, more than 130 studies have linked BPA to breast cancer, obesity, and other disorders. In 2007, a group of 38 independent NIH-funded investigators concluded there was strong cause for concern that exposure could result in cancer and early puberty. A 2008 study found that adults with higher urinary BPA levels had elevated rates of heart disease, diabetes, and liver abnormalities. Studies also suggest that BPA may interfere with cancer treatments.”
Although the Food and Drug Administration (FDA) ruled in 2008 that BPA is safe even for infants (Letter from Stephen R. Mason, Acting Assistant Commissioner for Legislation, Food, and Drug Administration, to Rep. John D. Dingell, Chairman, House Committee on Energy and Commerce, 2008 Feb 25), Canada banned its use in baby bottles and infant formula cans the same year. More than 20 states (e.g., MN, CT, CA) and a number of municipalities in the U.S. (e.g., Chicago; Suffolk County, NY) are following suit with proposed or enacted BPA bans.
Ironically, the Panel Report page on BPA includes a pull out quote from Jeanne Rizzo of the Breast Cancer Fund, one of the panelists at the East Brunswick Meeting:
“…we have companies that are formulating products in the United States that are different from those in Europe because there is no regulation [in the United States] requiring the more stringent standards.”
The report then launches from discussing BPA bans into an endorsement of the European Union’s REACH legislation, which regulates chemicals according to the precautionary principle.
But bizarrely, the report fails to mention that under these stringent standards the EU declared BPA safe in risk assessments conducted in 2006 and 2008, and has explicitly criticized all the evidence marshaled by the panel as evidence of the chemical’s danger.
In other words, the panel’s claim that we need European precautionary regulation of chemicals such as BPA ignores the fact that the EU has refused to ban BPA on precautionary grounds. (It’s worth noting that when STATS surveyed almost 1,000 members of the Society of Toxicology, 69 percent did not favor the U.S. adopting the precautionary principle in regulating chemicals).
This contradiction is sustained by other highly selective and misleading statements. First, the claim that the BPA found in urine is biologically active is misleading. It omits the fact that the CDC found both inactive and active BPA – and that 98 percent was inactive. The active BPA was only found in 10 percent of samples. The CDC also noted that “finding a measurable amount of BPA in the urine does not mean that the levels of BPA cause an adverse health effect.” (See sidebar for more detail).
Second, the “group of 38 independent NIH-funded investigators,” known as the Chapel Hill Consensus, have repeatedly had their research rejected as being methodologically inadequate for the purposes of risk assessment, which resulted last year in the National Institute of Environmental Health Sciences tightening its requirements for research funding on BPA by adopting the criteria used by the EU and FDA to determine what counts as rigorous, reliable research for the purposes of risk evaluation (for more on this, click here).
The panel also seems unaware that the evidence of adverse effects and associations came through using injection as the route of exposure, something all regulatory bodies reject in the case of BPA, as it does not reflect how humans are exposed to the chemical. This is relevant to the claim that BPA is a carcinogen, as noted by the toxicologist Calvin Willhite, lead author of NSF International’s calculation of a reference dose for BPA:
"[A]ll of the observations of changes in the female rodent mammary gland associated with BPA exposure were made after subcutaneous injections (e.g., Biology of Reproduction, Volume 65, pages 1215-1223, 2001; Congenital Anomalies, Volume 41, pages 187-193, 2002; Endocrinology, Volume 148, pages 116-127, 2007; Reproductive Toxicology, Volume 18, pages 803-811, 2004).
In contrast, the U.S. National Toxicology Program in 1982 [Carcinogenesis Bioassay of Bisphenol A (CAS No. 80-05-7) in F344 Rats and B6C3F1 Mice (Feed Study), Technical Report No. 215] concluded based on the results of lifetime BPA feeding studies that 'there was no convincing evidence that bisphenol A was carcinogenic for F344 rats or B6C3F1 mice of either sex.'"
He also noted that “since there was no indication whatsoever of preneoplastic or neoplasic changes in the mammary gland of the rats and mice after lifetime ingestion of very high BPA doses (to as much as 148 milligrams/kilogram per day in rats and 1,900 milligrams/kilogram per day in mice), the suggestion that somehow BPA injection studies in rodents are directly relevant to human health is without empirical support.”
Given that the chairman of the President’s panel, Dr. LaSalle Leffall, a professor of surgery at Howard University College, is also a past chair of the Susan G. Komen for the Cure, it is ironic that Dr. Leffall seems unaware that the Komen organization recently has concluded that "at this time, there is no evidence to suggest a link between BPA and risk of breast cancer."
As for the 2008 study that, as the panel notes, “found that adults with higher urinary BPA levels had elevated rates of heart disease, diabetes, and liver abnormalities,” Lang et al. was rejected as unusable by the European Food Safety Authority as it was a cross sectional study and couldn’t determine cause and effect. It was also criticized by Dr. S. Stanley Young, Assistant Director of Bioinformatics at the National Institute of Statistical Sciences, who noted that given there were nine million ways the data used by Lang et al. could be interpreted, the likelihood of a chance association was high (for more on this, and statistical problems with follow up study, click here).
In responding to criticism of the panel report from the American Cancer Society, Dr. Leffall told the New York Times that "This is an evenhanded approach, and an evenhanded report…We didn’t make statements that should not be made."
It is clear that, at least with regard to BPA, the panel was not even-handed or accurate about the evidence but highly polemical– and this raises questions as to what else might have been selectively or inaccurately reported as part of its overall argument about environmental cancer risks. As Dr. Michael J. Thun, the American Cancer Society's vice president emeritus for epidemiology and surveillance told NPR, the panel report presented only “one side of a scientific debate that has continued for almost 30 years.”
It is to the media’s credit that soon after the panel report was leaked to the New York Times columnist Nick Kristof, many reporters sought out the other side. But surely this is a terrible way to advise the President on cancer. Perhaps it is time for the President’s Cancer Panel to be folded into the National Academy of Sciences, which might ensure greater expert representation, greater attention to detail, and greater reliance on primary research in discussing these important matters. While it is important to hear minority viewpoints in any field of scientific research, the exclusion of the majority prevents the very testing of assumptions and data that constitutes the scientific method.