Glyphosate is the active ingredient in the pervasive herbicide Roundup, and its usage in agriculture has increased exponentially in the United States over the past two decades, in step with an alarming increase in the incidence of a long list of debilitating diseases and conditions, including diabetes, obesity, autism, Alzheimer’s disease, Parkinson’s disease, kidney disease, intestinal infection, pancreatic cancer, thyroid cancer, and many others.1 While correlation does not always necessarily mean causation, there is no other chemical I can find used in agriculture that is so pervasive and has similarly increased dramatically in step with the dramatic increase in these diseases. That these diseases are becoming much more common is indisputable, and something is causing this disturbing pattern. I believe there is now sufficient evidence that glyphosate could cause these diseases to support a causal relation in the observational trends. I hope you will agree with me after reading this chapter.
The choice of Roundup over other herbicides is based on its status as a nonspecific herbicide (that is, it kills all plants except those that have been genetically engineered to resist it) and, especially, its reputation as being practically nontoxic to humans. Monsanto, glyphosate’s original producer, was able to convince regulators back in the 1970s that it has very low toxicity to animals, in part using the argument that its main mechanism of toxicity to plants was based on its suppression of an enzyme in the shikimate pathway, ESPS synthase, which human cells never produce. This argument overlooks the fact that our gut microbes do possess the shikimate pathway, and they use this metabolic pathway to produce many vital nutrients that our own cells depend upon them to provide. The recent explosion in research papers on the gut microbiome attests to the fact that our gut microbiome today is chronically disrupted, and I think glyphosate plays a major role in this pathology.
A seminal paper by Seralini et al., first published in 2012 in the journal Food and Chemical Toxicology2 and later republished in the journal Environmental Sciences Europe3 after an ill-founded retraction by the original journal’s editors, involved a long-term study of rats exposed to very small doses of glyphosate over their entire lifespan. One of the important realizations that comes out of this study is that glyphosate is a slow kill. After the rats had been exposed to glyphosate for three months, there were no significant differences in the health status between the exposed rats and the controls. The agrochemical industry has declared that toxicity studies don’t need to go beyond three months, and nearly all of their reported studies are restricted to this maximum duration. Clearly, the toxicity of glyphosate could be missed altogether with such a strategy, convenient for keeping the chemical on the market.Seralini’s rats that were exposed to low doses of glyphosate eventually developed huge mammary tumors, kidney disease, liver disease, reproductive disorders, and early death. It can be supposed that disruption of the gut microbiome is a rather indirect mechanism of harm to the host and therefore takes more time to manifest as disease. However, I have come to believe that something much more insidious is going on, which over time results in an accumulation of glyphosate embedded in various proteins throughout the body.
The toxicologist Anthony Samsel and I have published a series of six papers together on glyphosate and disease. Remarkably, we had published four of these papers before we came to realize that glyphosate could be substituting for the coding amino acid glycine during protein synthesis by mistake. Glyphosate is in fact a glycine molecule, except that a hydrogen atom normally bound to the nitrogen atom has been displaced by a methyl phosphonyl group, as illustrated in Figure 1. Part of glyphosate’s toxicity has been presumed to be through its action as a glycine analogue. Glyphosate has been shown to excite NMDA (N-methyl-D-aspartate) receptors in rat hippocampus, and the argument is that it binds to the glycine-binding site in the receptor, pretending to be glycine.4 In fact, a paper suggesting that glyphosate might be useful as a cancer drug has argued that its mechanism of toxicity could be through its action as a glycine analogue to suppress glycine synthesis in tumors.5 Glyphosate disrupts the first step in the synthesis of chlorophyll, and this is probably in part because it displaces glycine as the substrate.6 However, the enzyme that catalyzes this step has a highly conserved glycine-rich stretch that could be susceptible to glyphosate substitution, further contributing to this observed effect.7