Do No Harm, With Weedkillers

Organoids enter the debate over hefty jury awards, while the scientific jury is still out

DNA evidence forever changed criminology by exonerating innocent people. Yet it has limitations because the absence of DNA does not always mean defendants were not at the crime. “As is its biological wont, DNA has an evolving role in the justice system,” one expert observed. Not cast in stone — but rather, “evolving.”

Organoids are a new branch on the DNA-as-evidence tree, and like its legal cousin, organoid research has an evolving role in medical science. It’s edging into a controversy around the chemical “glyphosate,” a weedkiller used at a rate of 280 million pounds annually in the U.S., and more worldwide.

Human stem-cell-generated organoids contain their donors’ DNA, and can reveal cell activity in ways never before possible. With stem cells as their seeds, organoids grow in lab dishes into tiny replicas of human organs. Twins of the real thing, they are mini-kidneys, mini-lungs, mini-stomachs and more. An organoid is literally a chip off the old block. As such, they can replace human volunteers and lab animals, for testing purposes.

Organoids are akin to automobile crash-test dummies that show researchers exactly what would happen to humans if they drive into a wall. Or inhale a weedkiller.

Glyphosate is the chief ingredient in Roundup® Weed Killer. Non-Hodgkin lymphoma patients who claim that repeated exposure to Roundup® fueled their illnesses have been suing Roundup®’s long-time manufacturer, Monsanto — now owned by Bayer Pharmaceutics Company — alleging that the U.S. Environmental Protection Agency’s approval of Roundup® was erroneous and dangerous. Claims against the manufacturer include that the company:

· Hid the conclusions of a prominent toxicologist that glyphosate damages genes and causes mutations

· Faked findings of a 1980s study in order to fuel the EPA’s decision that glyphosate is not cancer-causing

· Knew that inferior lab practices laced the sole study on which EPA approval was based.

Medical experts are contradicting each other. The Europe-based World Health Organization says glyphosate is likely carcinogenic. Some WHO officials say the EPA approval is based on shoddy experiments. The EPA says WHO’s stance is based on shoddy experiments.

Juries of peers forge burly awards

While expert disagreements swirl, a 2018 U.S. court awarded $39 million to a cancer patient who had used hundreds of gallons of Roundup® while working as a groundskeeper. A 2019 award of $80 million is due to a patient living in remission from Stage 3 Non-Hodgkin lymphoma since 2015. He persuaded a jury that his 26 years of using Roundup® on his rural property caused lymphoma. The trial in the case of a married couple who are both in remission following chemotherapy for non-Hodgkin lymphoma began in March 2019. They claim they used Roundup® on their property for decades and that the probability of them both developing the same cancer is 1 in 20,500.

There are reportedly more than 11,000 similar lawsuits being prepared and filed. Bayer plans to appeal losses and to fight every claim, as well as to get Roundup® removed from lists of possible carcinogens. Bayer points to 800 studies showing how glyphosate kills only certain molecules in weeds — molecules that do not exist in animals or humans. That is why the company deems it safe.

Weeding out the facts

Weeds have historically been a stubborn threat to world food supplies. Inadequate weed control lowers crop yields, so pausing pesticides could cost more than $6 billion worldwide and breed food shortages. Some kind of weedkilling, toxic or non-toxic, has been a necessity.

Dr.Geoffrey Kabat, cancer epidemiologist and author of 150 scientific papers, describes WHO’s labeling of glyphosate a likely carcinogen as inaccurate, and calls it a “Glyphosate-gate scandal.” A 2018 review of research was authored by Robert E. Tarone, a mathematical statistician at the U.S. National Cancer Institute for 28 years, and Biostatistics Director at the International Epidemiology Institute for 14 years. “The classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence,” Tarone writes. “Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents.” Canada’s official policy as of 2019 is: “No pesticide regulatory authority in the world currently considers glyphosate to be a cancer risk to humans at the levels at which humans are currently exposed.”

An older, 2004 study found that U.S. farmers — and their children who helped with mixing, loading, or application — had glyphosate in their urine, but not at dangerous levels as defined by the EPA. “Nonetheless, it is advisable to minimize exposure to pesticides, and this study did identify specific practices that could be modified to reduce the potential for exposure,” the researchers wrote, in a possible nod to ambivalence around the EPA’s definition of dangerous to children.

A 2016 investigation found glyphosate residue in 93 percent of urine samples from voluntary public testing in the U.S. Critics point out this just shows that humans excrete toxins via urinating, like any contaminant.

Alternate views

One 2018 finding of glyphosate in the urine of pregnant women suggests it could place pregnancies and newborns at risk. Another 2018 study found glyphosate sprayed on plants left bees unable to pollinate, which differs from older studies that found no danger to animals. A 2019 statistical analysis reported by U.S. scientists found “a compelling link” between glyphosate and Non-Hodgkin lymphoma.

Is there more glyphosate in plants, food, rivers and soil — and on farmers’ skin and nostrils — than ever before? Could this explain the differences in expert opinions? According to the U.S. National Institutes of Health, the use of glyphosate has shown “a dramatic increase” over time. Two-thirds of all glyphosate used in the four decades from 1974–2014 was used in those last ten years — from 2004 to 2014.

In 2017, an international team including U.S. and European scientists concluded that use is constantly increasing and expanding. As a result, levels of glyphosate found in food, soil or water may be higher now than during the time of studies conducted 40, 20 or 10 years ago.

They also pointed out that glyphosate, when combined with other Roundup® ingredients, may be more toxic than glyphosate alone. Many older studies looked at glyphosate alone, not in its usual state of being mixed with other weedkillers. The team compared older studies to newer ones, and found greater evidence of toxicity in the genes, livers, kidneys, brains and hearts of some animals, as well as of non-Hodgkin lymphoma and endocrine disruption in humans. They concluded that “state-of-the-art approaches are needed to better elucidate the effects of glyphosate.”

“Many assumptions have been made about the safety of glyphosate that are now being actively questioned,” one U.S. expert said in April 2019. “We will see an explosion of information about glyphosate, and it’s about time. We’re really playing catch-up on this one.”

Enter organoids

Just as DNA evidence changed criminology, because it was a new method not available in previous years or centuries, organoid evidence can change glyphosate research. Current medical studies employ cutting-edge techniques that were not available in the 1970s or 1980s.

Researchers at Wake Forest Institute for Regenerative Medicine found that organoids are effective for testing glyphosate on human tissue. Their 2018 study looked at the impact of toxins, including glyphosate, on liver organoids and cardiac organoids. Although organoid-testing has limitations, they found that “organoids have significant utility to be deployed in additional toxicity screening.” All their tests found toxicity in the organoids.

In 2018, a Duke University Biomedical Engineering study covered the limitations organoids will have as their use scales up, as well as their potential contributions. The conclusion was that organoid research can provide “unbiased” testing that is needed to “understand the mechanism of action of environmental toxins. . . While few studies have examined environmental pollutants, studies with drugs demonstrate the power of (organoids) to assess toxicity as well as mechanism of action.”

Unprecedented Opportunity

A team of scientists at the Harvard Stem Cell Institute explained in a 2015 study how cutting-edge advances increase organoids’ usefulness: Organoids provide a “more advanced tool” and are an “unprecedented opportunity to monitor” cell behavior.

Sometimes it can seem like medicine could use some new clickbait: “Game-Changer,” “Breakthrough” and “Cure” all suffer from headline fatigue. Breakthroughs are actually the new normal. Innovations like organoids are often vastly superior to what scientists had to work with years ago. Reassessments, updates, revisions and discoveries are happening not because cells or proteins or molecules have changed, but because the methods used to understand them are changing.

“As is its biological wont, DNA has an evolving role in the justice system.” And as is their biological wont, organoids have an evolving role in the Roundup® debate.