Day 15 – The EPA Ain’t The Ten Commandments
It’s freezing and drizzly again today. Canadians, listen up. One of your peeps is in the house.
The courtroom itself is rather bland, but it is host to quite a grand event when a witness is called. The witness stands outside of the courtroom until officially invited to come up to the bench. It reminds me of a bridal procession, watching someone enter through the double doors in the back of the courtroom, step down the isle of the viewing section, meander in front of the jury, and step up to the witness box. I often wonder if people ever trip – particularly since any normal person would be nervous. Maybe that embarrassing spectacle is on reserve for me if I am ever an expert witness in a trial.
Today, Mr. Griffis calls expert witness Dr. Warren Foster and we all look towards the door. A tall, corporatey-looking man brazenly struts in through the double doors and all eyes are on him. Alas, he is a merely a decoy and takes his seat in the Monsanto crowd. A few moments later, Dr. Foster walks in, quite the opposite of brazenly. He looks much more like the visiting scientist; this must be the guy.
Dr. Foster emerges from the double doors slowly, staring straight ahead, and walking with short, deliberate paces and an overly-upright posture. Because I’m in the aisle, I get an up-close view of his very long, blonde and gray ponytail that is pulled together in a Goody brand hairband. The strands look highlighted, though I can’t imagine this particular man going to such aesthetic lengths. He wears a suit and tie, with a pin of some kind on his lapel. Throughout the day, I try to read what that pin says – but I begin to look like a crazy lady in staring intently at his chest. So, I’ll just conclude that it is a pin from an organization that he thinks is neat.
At home, I can imagine him in the academic uniform of choice: mockturtleneck, high-waisted Levis with a braided leather belt, and well-worn Birkenstocks or non-name-brand white running shoes. But on this big day, he looks sharp! He also seems like a really nice guy.
THE TESTIMONY OF DR. WARREN FOSTER
Monsanto attorney Mr. Griffis (who judge Bolanos often incorrectly calls Mr. Griffith) asks Dr. Foster to discuss his biography.
Dr. Foster specializes in reproductive and developmental biology and toxicology, with a particular interest in endometriosis. He has a BS in Biology from the University of Guelph in Ontario, Canada. Foster also has a masters from Ontario Vetrinary College (at the U of Guelph) and a PhD in Medical Sciences from McMaster University. He has been a professor at McMaster for thirteen years. I can completely see him as a family vet; I wonder why he shifted directions.
When McMaster is mentioned, the juror who is a scientist nods enthusiastically and smiles. I wonder if that is where she went to college too.
Dr. Foster also worked at Health Canada – the US EPA equivalent – for over a decade. At Health Canada, he was involved in the design and conduct of animal carcinogenicity studies and helped regulators in assessing data. He was also the Health Canada representative to the Organization for Economic Cooperation and Development (OECD), in which he met with global parties every nine months in Paris to develop and share guidelines across countries for chemical assessment.
Well what do you know, we have a man who has worked for the regulatory body of Canada. Naturally, this runs through my mind again – yet another time we introduce the views of a foreign environmental regulatory agency but still cannot discuss the California EPA:
Dr. Foster is also an expert in translational toxicology. A translational toxicologist is someone who looks at animal studies and animal physiology and can determine if the findings are translatable to humans.
Funding for his studies comes primiarlily from the Canadian Institute of Health Research (similar to the US NIH), the Natural Sciences Council, the American Chemistry Counsel, and the pharmaceutical industry. Foster has served on IARC in evaluating three chemicals. He has published more than 180 articles and several book chapters, and was elected to the prestigious Canadian Academy of Health Sciences.
Griffis calls for expert designation, but as per usual, Wisner has a few clarifying questions first.
Wisner asks whether a PhD in Medical Sciences is an MD, which it is not. Wisner clarifies Foster’s timeline between being hired by Monsanto attorneys and serving on IARC. As it turns out, he had already agreed to work with the attorneys before voting at IARC. BUT – the chemicals under review at IARC were of no relation to glyphosate.
Dr. Warren Foster is named an Expert in the Design, Evaluation and Interpretation in Long term Rodent Carcingenicity Studies.
DIRECT TESTIMONY OF DR. WARREN FOSTER
Dr. Foster is paid $250/hour by Monsanto attorneys and he estimates total billing will be around $60K – $65K. I hope for his sake that those are American dollars. If he ever reads this blog, he will realize that he should ask for a raise.
In opening, Dr. Foster shares that he studied and reviewed all twelve rodent studies that Dr. Portier reviewed on the exemplary presentation boards. “In reviewing the studies individually and together, I concluded that there are no compound-related effects in any of these studies.”
And there is the crux of Plaintiff’s argument today. This message is critical for Monsanto, because the credibility of the Plaintiff’s animal carcinogenicity claims hinges on these studies, particularly that controversial 1983 Knezevich & Hogan study that showed kidney carcinomas and adenomas in CD-1 mice.
Dr. Foster regularly works in rodent testing, so he shares with the jury how to setup, analyze and draw conclusions from a regulatory-agency-approved animal carcinogenicity study. Like Tuesday’s blog, I will do a deeper dive given the detailed powerpoints that Monsanto presents. You will find those details under the “In case you care” sections throughout this post.
IN CASE YOU CARE: #1: REQUIREMENTS FOR REGULATORY CARCINOGENICITY STUDIES
- Mice or rats receive control or test substance daily
- The groups include one control, one low, one medium, one high dose group
- Usually 50 animals per sex per dose group (400 animals)
- High dose group should be 1000 mg/kg/day according to the OECD Guidelines for Testing Chemicals 453 – Combined Chronic Toxicity/Carcinogenicity Studies The scientist tries to get a dose high enough to confirm an effect on the animal. Foster claims that no human will ever see levels above 1000mg/kg/day, so 1000 is plenty for the high dose group.
IN CASE YOU CARE #2 – REQUIREMENTS FOR REGULATORY CARCINOGENICITY STUDIES
- Study duration is 18 months for mice and 24 months for rats
- Animals observed daily for signs of toxicity and appearance of neoplastic lesions
- Animals that die spontaneously and those sacrificed at the end of the study undergo full necropsy, the pathological examination of a corpse (aka autopsy for animals)
TESTING OF THE FORMULATED PRODUCT ROUNDUP
The much heated topic about the lack of studies on the formulated Roundup product – as opposed to pure glyphosate – continues. Foster says that a test on formulations has not been done with any pesticide. He claims that it would be challenging to conduct such a study because the toxic effects of the surfactants would kill the animals before showing carcinogenicity of the compound. It would wreck their tiny little intestines and gut, because the mode of exposure is through food.
Well that’s appetizing. Public service announcement – eat organically when possible. Over time, toxins accumulate.
There is no harmonized agreed upon guideline for testing pesticide mixtures. Foster and Griffis conclude that, therefore, Monsanto can’t realistically conduct such a study.
IN CASE YOU CARE #3: SLIGHTY GORY DETAILS OF ANIMAL TESTING, Rated PG-13
Rodent studies are done to screen a compound like glyphosate to determine whether any tumors are showing up “from nose to toes.” Foster calls it, “Going on a fishing expedition. No idea what we are going to get.” After getting 40 tissue samples from 400 rodents, 16000 different date points are collected.
Foster calls these “nightmare studies” because a team spends a whole week weighing, sacrificing, and taking notes. When the pathologists and biochemists do their thing, they do not know which dose level any particular rodent was given, so as to avoid any bias.
The jury is now taught about spontaneous tumors in order to preview why there likely were kidney tumors in the control group in the controversial 1983 mouse study.
Griffis asks Foster if it is possible to see tumors in all groups, including control. Foster says: “Yes, it is not uncommon to see spontaneously occurring tumors.”
When describing spontaneous tumors, Foster says:
- They occur naturally in all dose groups and sexes
- The incidence of spontaneous DNA mutations increases with age as DNA repair mechanisms deteriorate and animals get older
- A toxicologist must differentiate between spontaneous tumors and potentially compound-related tumors
When asked what might cause these tumors, Foster points to radiation, food, and many other non-glyphosate potential causes.
HOW A TOXICOLOGIST DETERMINES IF THERE IS A REAL EFFECT
Foster dishes what he looks for in a quality study:
- Compliance with regulatory guidelines
- Consistency within and across outcome measure (AKA sanity check)
- Dose response – expect it to be linear, or upwards and then plateau
- Contemporaneous control rates
- Historical control rates
- Neoplastic progression
- Systemic toxicity
The standard practice in a study is to lay out, before the study, what statistical practices will be ultimately run on the data. The toxicologist doesn’t “want to shop for the statistical procedure that gives us the answer we want.” Apparently, Foster knows of some scientists who look at data and see which calculation gives the statistical significance they are looking for. As an academic, Foster says that he is dependent on being able to publish his work, and shopping for statistical significance (also known in the statistics world as “p-hacking”) would negatively impact his ability to get the next grant.
In implying that Portier is shopping for statistical significance, Griffis asks if a study concludes negatively, and there are no statistically significant findings, is it “proper to run new statistical tests to see if you can find a statistically significant result?” Foster answers no.
RODENTS ARE NOT TINY PEOPLE
I know an odd man who works at PetSmart who would disagree.
Monsanto is subtly pushing the idea that even if a test is statistically significant and positive in a rodent carcinogenicity study, it’s quite limited in its actual application to humans. Remember, Foster is a “Translational Toxicologist.”
As Foster sees it:
- Rodents are used in carcinogenicity studies primarily because they are cheap, plentiful, and have short lifespans
- There are major biological difference between rodents and people
- Although both rodents and humans get get cancer, some rodent tumors develop and progress differently than human cancers.
He concludes that there are known rodent carcinogens that are not human carcinogens, but not known human carcinogens that are not rodent carcinogens. That statement feels very convenient.
OPP REPORT AND TUMORS
Griffis shows the jury EPA’s OPP Glyphosate Issue Paper from Septemteber 2016.
The report says that “Based on the weight-of-evidnece approach, the agency has determined that any tumor findings observed in the rat and mouse carcinogenicity studies for glyphosate are not considered treatment-related.
Foster comments that the high dose group in the 1983 study is so high that it is not relevant for humans. He also says that he fully concurs with the EPA’s analysis and decision.
THE GEORGE STUDY
“The George Study” is the 2010 painted mouse study Studies on Glyphosate-Induced Carcinogenicity in Mouse Skin: A Proteomic Approach.
Do you remember this study? After applying Roundup on mice, the study shows that glyphosate has tumor-promoting potential in skin carcinogenesis.
Griffis asks Foster his opinion on the study.
Actually, Griffis speaks so incredibly softly throughout the Direct, that I’m not entirely sure that is what he asked him. I mean, it was so soft that the mic often doesn’t register his voice.
Foster says that the study is weak because they went to their local market in India and purchased Roundup there, instead of getting a certified product straight from Monsanto. He has suspicions that no one can be certain what was in the local Indian market concoction.
Additionally, they didn’t do a histopathological study – a formal review by a pathologist – of the lesions. Surgeons and pathologists often disagree. Foster says it is not uncommon in clinical studies to get a biopsy and the surgeon says it is cancer and the pathologist says it’s not.
This happened to my uncle last year – he had a huge tumor in his large intestine and, after operating, the surgeon told him it is likely cancer. Well, it came back benign, but only after he died of complications that were likely aggravated by stress and anxiety in the meantime.
Foster concludes that the George study is inadequate when following the EPA’s OPP guidelines.
FOSTER’S CRITIQUE OF DR. PORTIER’S ANALYSIS
Right away, Foster dismisses all of the rat studies that Dr. Portier highlighted. He says that there is no evidence of anything that Health Canada would find as evidence of a carcinogenic finding.
Next, we look at the mice studies as per Portier.
Monsanto has duplicated his chart in large poster form, but with a dramatic interactive feature. One of the associates must have spent hours putting together this poster board. Each little square is its own glossy thick card. Griffis goes to the side of the bench and returns with a small plastic trashcan.
First, Kumar 2001 is entirely dismissed because of a reported virus and parasite in the study mice.
One by one, Foster tears off and throws away each finding in each study, until the once grand poster is left feeling sad and empty, and the garbage can happy and full.
I can’t tell if the garbage can effect is successful or cringeworthingly cheese.
THE CROSS EXAMINATION OF DR. WARREN FOSTER
Wisner is on fire today, on fire but with a pleasant disposition. I appreciate that because while I don’t agree with what Foster concludes, he seems like a kind man.
Wisner asks him if he is a statistician. Foster says he is not, but numbers are important, “especially on my pay check!” The jury laughs. I feel sad for him because while he was just cracking a lighthearted joke, the timing probably wasn’t great as Monsanto is paying him $60K to say that the 1983 mouse study showed no cancer.
I’m going to whip through Wisner’s points, because there were so many that could stand their own respective blog entries. It’s overwhelming and 1:30am.
- Wisner calls out Foster for stating that: “Animal models are a poor model for studying cancer.” Foster says that some animals could be good for studying pathogenesis. Wisner stresses that Johnson’s cancer is a T-Cell lymphoma which can manifest anywhere in the body. Johnson’s is cutaneous. When trying to look at lymphoma, it would be weird to look at a single organ site when assessing carcinogenicity when it could be anywhere in the body. Moreover, Wisner stresses that if something isn’t really a carcinogen, we would expect that any tumors found would be similar to control, not a dose response increase outside of the normal range.
- Wisner takes the opportunity to point out that the first legit mouse study was in 1983, even though Roundup came on the market in 1976.
- Foster relied upon the Greim report 2015 to provide data for his own evaluation. Wisner asks Foster if he knows that co-author David Saltimras is a Monsanto employee or that another co-author is a member of the industry-supported Glyphosate Task Force. Wisner explains that the Glyphosate Task Force is a group of manufacturers that got together and “created data.” Foster denies that they “created” the data, though I do think that he is a bit surprised by their affiliation with Monsanto.
- Regarding the Kumar study, it was the same Monsanto co-authored Greim paper that suggested a viral infection confounding the data and making it of inadequate quality to be included in the animal data assessment. Word of the virus also spread globally via former US EPA official Jess Rowland, who many have thought actively colluded with Monsanto.
- Wisner walks through the timetable of the 1983 Knezovich and Hogan mouse study that showed concerning kidney tumors. As we know, a questionable control kidney tumor popped up when Monsanto’s hired pathologist took a looksee. After Wisner rehashes details, Foster says that he is “Not privy to the back and forth.”
Wisner spends a long time delving into to the Scientific Advisory Panel Report on glyphosate from March 2017. The SAP was brought in to provide an independent perspective on the ongoing controversy around the EPA’s evaluation of glyphosate carcinogenicity. In the report, “the panel recommends that the EPA clearly explain why historical control rates were used in some analyses and not others.” Also that: “Many panelists concluded that the use of historical control information in the issue paper does not adhere to EPA Cancer Guidelines.”
In response, Foster defends the EPA: “Yes, these are guidelines…not the Ten Commandments!” Furthermore, he doesn’t find it unreasonable “to deviate on occasion.” He does not think that the SAP is saying the EPA “got it wrong,” just that they could “do it better.”
UMMMMM – does he really believe that? I’m not so sure.
The Monsanto attorneys do not look particularly pleased as the day comes to a close. Today was destined to be challenging no matter who they brought in to talk animal studies. The evidence just makes all of the EPA evaluations of glyphosate look exceptionally suspicious.
My takeaway today is that Foster tried to represent the EPA and Monsanto as best he could, but he really seems like a nice-guy scientist who is concerned about his reputation and enjoys his life as an academic in Canada. By the very end of the day, I almost wondered if Wisner had brought Foster around to his way of thinking. Today was a win for the Plaintiff.
There are more details from a disagreement that Wisner and Foster had over control data lymphoma ranges from the Wood 2009 study that I don’t have access to. Ultimately, Foster concedes that he has overestimated the average percent of positive controls that are expected in an animal study. I will check on the transcripts when they become available so as not to misspeak on this topic.
More witness testimony! Monsanto estimates they will rest on Monday, which means that Closing Arguments may be Tuesday but could also be Wednesday. I’ll keep everyone updated! Start sending positive vibes to San Francisco!!
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