A
deep dive into dead mice as Monsanto goes to
court.
By
Carey Gillam for Environmental
Health News
Call
it the case of the mysterious mouse tumor.
It’s
been 34 years since Monsanto Co. presented U.S. regulators with a seemingly
routine study analyzing the effects the company’s best-selling herbicide might
have on rodents.
Now, that study is once again under the microscope, emerging
as a potentially pivotal piece of evidence in litigation brought by hundreds of
people who claim Monsanto’s weed killer gave them cancer.
Tissue
slides from long-dead mice in that long-ago research study are being
scrutinized by fresh eyes as an expert pathologist employed by lawyers for
cancer victims looks for evidence the lawyers hope will help prove a cover-up
of the dangers of the weed killer called glyphosate.
Glyphosate,
which is the active ingredient in Monsanto’s branded Roundup products, is the
most widely used herbicide in the world, and is applied broadly in the
production of more than 100 food crops, including wheat, corn and soy, as well
as on residential lawns, golf courses and school yards.
Residues
have been detected in food and human urine, and many scientists around the
world have warned that exposure through diet as well as through application can
potentially lead to health problems.
What
the expert finds, or doesn’t find, is expected to be key evidence in hearings
slated for the week of Dec. 11 in
dozens of consolidated
cases being overseen by a federal judge in San Francisco.
Rewind to 1983
Monsanto,
as well as many other scientists and regulatory bodies, have defended
glyphosate’s safety. They say research showing a cancer connection is flawed
and hundreds of studies support its safety.
And
yet—rewind to July 1983 and a study titled “A Chronic Feeding Study of
Glyphosate (Roundup Technical) in Mice.”
Following
the document trail that surrounds the study offers an illuminating look into
how science is not always clear-cut, and the lengths Monsanto has had to go to
in order to convince regulators to accept scientific interpretations that
support the company’s products.
The
two-year study ran from 1980-1982 and involved 400 mice divided into groups of
50 males and 50 females that were administered three different doses of the
weed killer or received no glyphosate at all for observation as a control
group.
The
study was conducted for Monsanto to submit to regulators. But unfortunately for
Monsanto, some mice exposed to glyphosate developed tumors at statistically
significant rates, with no tumors at all in non-dosed mice.
A February 1984
memo from Environmental Protection Agency toxicologist William
Dykstra stated the findings definitively: “Review of the mouse oncogenicity
study indicates that glyphosate is oncogenic, producing renal tubule adenomas,
a rare tumor, in a dose-related manner.”
Researchers
found these increased incidences of the kidney tumors in mice exposed to
glyphosate worrisome because while adenomas are generally benign, they have the
potential to become malignant, and even in noncancerous stages they have the
potential to be harmful to other organs.
Monsanto
discounted the findings, arguing that the tumors were “unrelated to treatment”
and showing false positives, and the company provided additional data to try to
convince the EPA to discount the tumors.
But
EPA toxicology experts were unconvinced. EPA statistician and toxicology branch
member Herbert Lacayo authored a February 1985 memo
outlining disagreement with Monsanto’s position.
A
“prudent person would reject the Monsanto assumption that Glyphosate dosing has
no effect on kidney tumor production,” Lacayo wrote. ”Glyphosate is suspect.
Monsanto’s argument is unacceptable.”
Eight
members of the EPA’s toxicology branch, including Lacayo and Dykstra, were
worried enough by the kidney tumors in mice that they signed a consensus review of
glyphosate in March 1985 stating they were classifying glyphosate as a Category
C oncogen, a substance “possibly carcinogenic to humans.”
Research rebuttal
That
finding did not sit well with Monsanto, and the company worked to reverse the
kidney tumor concerns.
On
April 3, 1985, George Levinskas, Monsanto’s manager for environmental
assessment and toxicology, noted in an internal
memorandum to another company scientist that the company had
arranged for Dr. Marvin Kuschner, a noted pathologist and founding dean of the
medical school at the State University of New York at Stony Brook, to review
the kidney tissue slides.
Kushner
had not yet even accessed the slides but Levinskas implied in his memo that a
favorable outcome was assured: “Kuschner will review kidney sections and
present his evaluation of them to EPA in an effort to persuade the agency that
the observed tumors are not related to glyphosate,” Levinskas wrote.
Notably,
Levinskas, who died in 2005, was also involved in efforts in the
1970s to downplay damaging findings from a study that found
rats exposed to Monsanto’s PCBs developed tumors, documents filed in PCB
litigation revealed.
Kuschner’s
subsequent re-examination did —as Monsanto stated it would—determine the tumors
were not due to glyphosate.
Looking
over slides of the mouse tissue from the 1983 study, Kuschner identified a
small kidney tumor in the control group of the mice – those that had not
received glyphosate. No one had noted such a tumor in the original report.
The
finding was highly significant because it provided a scientific basis for a
conclusion that the tumors seen in the mice exposed to glyphosate were not
noteworthy after all.
Additionally,
Monsanto provided the EPA with an October 1985 report from a “pathology working
group” that also rebutted the finding of the connection between glyphosate and
the kidney tumors seen in the 1983 study.
The
pathology working group said “spontaneous chronic renal disease” was “commonly
seen in aged mice.” Monsanto provided the report to the EPA stamped as a “trade
secret” to be kept from the prying eyes of the public.
The
EPA’s own scientists still did not agree, however. An EPA pathologist wrote in
a December 1985 memo that additional examination of the tissue slides did not
“definitively” reveal a tumor in the control group.
Still,
the reports by the outside pathologists brought into the debate by Monsanto
helped push the EPA to launch a reexamination of the research.
And
by February 1986 an EPA scientific advisory panel had dubbed the tumor findings
equivocal; saying that given the tumor identified in the control
group by some pathologists, the overall incidences of tumors in the animals
given glyphosate were not statistically significant enough to warrant the
cancer linkage.
The
panel did say there may be reason for concern and noted that the tumor
incidences seen in the mice given glyphosate were “unusual.”
The
advisory panel told the EPA the studies should be repeated in hopes of more
definitive findings, and that glyphosate be classified into what the agency at
that time called Group D—“not classifiable as to human carcinogenicity.” The
EPA asked Monsanto for a repeat of the mouse oncogenicity study but Monsanto
refused to do so.
The company argued “there
is no relevant scientific or regulatory justification for repeating the
glyphosate mouse oncogenicity study.”
Instead,
the company provided EPA officials with historical control data that it argued
supported its attempt to further downplay the tumor incidences seen in the
worrisome 1983 study.
The
company said the tumors in mice appear “with some regularity” and were probably
attributable to “genetic or environmental” factors. “It is the judgement of
Monsanto scientists that the weight-of-evidence strongly supports a conclusion
that glyphosate is not oncogenic in the mouse.”
Monsanto
said repeating the mouse study would “require the expenditure of significant
resources... and tie-up valuable laboratory space.”
Feds fold
The
discussions between Monsanto and the EPA dragged on until the two sides met in November
1988 to discuss the agency’s request for a second mouse study
and Monsanto’s reluctance to do so.
Members
of the EPA’s toxicology branch continued to express doubts about the validity
of Monsanto’s data, but by June of 1989, EPA officials conceded, stating that
they would drop the requirement for a repeated mouse
study.
By
the time an EPA review committee met on June 26, 1991, to again discuss and
evaluate glyphosate research, the mouse study was so discounted that the group
decided that there was a “lack of
convincing carcinogenicity evidence” in relevant animal
studies.
The
group concluded that the herbicide should be classified far more lightly than
the initial 1985 classification or even the 1986 classification proposed by the
advisory panel.
This
time, the EPA scientists dubbed the herbicide a Group E chemical, a
classification that meant “evidence of non-carcinogenicity for humans.”
At
least two members of the EPA committee refused to sign the report, stating that
they did not concur with the findings. In a memo explaining the decision,
agency officials offered a caveat.
They
wrote that the classification “should not be interpreted as a definitive
conclusion that the agent will not be a carcinogen under any circumstances.”
Despite
the EPA’s ultimate conclusion, the mouse study was among those cited by IARC
for classifying glyphosate as a probable human carcinogen.
Indeed,
many other animal studies have similarly had questionable results,
including a 1981 rat study that
showed an increase in incidences of tumors in the testes of male rats and
possible thyroid carcinomas in female rats exposed to glyphosate and a 1990 study that
showed pancreatic tumors in exposed rats. But none have swayed the EPA from its
backing of glyphosate safety.
Christopher
Portier, who was an invited specialist to the IARC review of glyphosate and is
former director of the National Center for Environmental Health and Agency for
Toxic Substances and Disease Registry at the U.S. Centers for Disease Control
and Prevention, believes the evaluations applied to glyphosate data by
regulators are “scientifically
flawed” and putting public health at risk.
"The
data in these studies strongly supports the ability of glyphosate to cause
cancer in humans and animals; there is no reason to believe that all of these
positive studies arose simply by chance,” Portier said.
Monsanto fought the
plaintiffs’ request to view the mouse tissue slides, calling it a
“fishing expedition,” but was overruled by U.S. District Judge Vince Chhabria
who is overseeing the roughly 60 combined lawsuits under his purvey.
Monsanto
has confirmed that roughly 900
additional plaintiffs have cases pending in other jurisdictions.
All make similar claims – that Monsanto manipulated the science, regulators and
the public in ways that hid or minimized the danger posed by its herbicide.
“The
importance of the original kidney slides and the re-cut kidney slides is
immense to the question of general causation and played a critical role in the
EPA’s decision to re-categorize glyphosate…” the plaintiffs’ attorneys stated in a
court filing.
Plaintiffs’
attorney Aimee Wagstaff reiterated that in a recent court
hearing, telling Judge Chhabria that the events surrounding the 1983
mouse study “sort of dominoed,” and potentially are “extremely relevant” to the
cancer litigation.
Carey
Gillam is the Research Director at U.S. Right to Know and a veteran journalist
who specializes in coverage of food, agriculture and environmental issues.