Toxic Legacy, How the weedkiller glyphosate is destroying our health and the environment

Glyphosate is a very widely used general weed killer. Much of the public discussion about its safety is around whether it causes cancer. But Stephanie Seneff's book highlights all the other ways that glyphosate can damage our health.

Book cover for the book 'Toxic Legacy'
Book by Stephanie Seneff

Published by Chelsea Green, 2021

Glyphosate is about the only general weedkiller that can be used in the EU. It is used by ‘no-till’ farmers to kill vegetation before they sow a crop and by local authorities to keep our roads and pavements ‘weed-free’. It is also used on cereal crops such as wheat, just before harvest, to kill the plants so the grain dries and is more easily harvested. Many genetically modified crops, grown extensively in the USA but not in Europe, are engineered to be resistant to glyphosate – they are ‘Roundup Ready’, Roundup being the glyphosate-containing weed killer produced by Monsanto, who also developed the genetically modified corn, soya and other crops resistant to it. As a result of the widespread cultivation of these crops glyphosate use in the USA (where Seneff lives) has increased 15-fold since the 1970s. Glyphosate is considered to be safe. This is what Seneff disputes.

Much of the public discussion about the safety of glyphosate is around whether it causes cancer. But cancer is hardly mentioned in this book: the author wants to highlight all the other ways that glyphosate can damage our health. The book has a lot of detailed discussion of the various ways that glyphosate interferes with biochemical processes resulting in a variety of different health impacts. These impacts are not as dramatic as the obliteration of life that glyphosate brings about in living plants, but they constitute a significant burden of poor health and impairment. Senff, a research scientist at the Massachusetts Institute of Technology who since 2008 has been looking into the impact of nutritional efficiencies and environmental toxicants on human health, argues that increases in autism, diabetes, inflammatory bowel disease, kidney disease, liver disease, obesity, pancreatic cancer and thyroid cancer in the US are correlated with the rise in glyphosate use to such an extent that there is likely to be a causal link.

Glyphosate is an antibiotic and a chelator (a small molecule that binds tightly to metal ions) as well as a herbicide. For us glyphosate’s antibiotic effect means it kills bacteria in our guts which are susceptible to it, which unfortunately tend to be the more beneficial gut microbes that help us digest food and protect us from disease. Killing these bacteria allows less beneficial micro-organisms to flourish, some of which produce toxic metabolites that can have an impact on the brain. The changes in the gut microbiome can lead to inflammation and all the digestive problems that go with this. In the soil glyphosate disrupts the soil biota, inhibiting beneficial organisms such as nitrogen-fixing bacteria and promoting the growth of pathogenic fungi. Glyphosate’s action as a chelator means it may enable toxic metals such as aluminium and arsenic to get into tissues while it makes other metal ions unavailable for essential biological processes.

Glyphosate is thought to kill plants through its impact on the enzyme EPSP synthase. Enzymes are proteins, which are polymers of amino acids. EPSP synthase catalyses the synthesis of EPSP (5-enolpyruvylshikimate-3-phosphate) from PEP (phosphoenolpyruvate), which is a step in the shikimate pathway, the series of reactions that results in synthesis of the amino acids tryptophan, tyrosine and phenylalanine. The presumption that glyphosate is not toxic to humans arises because human cells do not have any of the enzymes of this pathway and cannot make these amino acids; they are known as ‘essential amino acids’ because we need to get them from our diet, though we are coming to realise that we also obtain them from the micro-organisms in our gut, micro-organisms that are killed by glyphosate. The standard view is that the phosphate of glyphosate binds at the site on EPSP synthase that is meant for the phosphate of PEP, thus blocking the binding of PEP and therefore the synthesis of EPSP and hence of the amino acids. However, molecules which are almost the same shape and size as glyphosate (shape is all important in biochemistry), but in which the nitrogen of glyphosate is replaced by an oxygen or a sulphur, do not inhibit EPSP synthase. Seneff argues that this is because glyphosate actually works not by competing with PEP for the binding site on EPSP synthase but by substituting for the amino acid glycine (see below) at a critical place in EPSP synthase: glyphosate is incorporated into the protein. This views is, apparently, controversial but I think she gives good arguments for it being the mechanism by which glyphosate has some of its effects.

How glyphosate substitutes for the amino acid glycine
Amino acids, the building blocks of proteins, all have an amino group (NH2) attached to a carbon which is attached to a carboxyl group (COOH). The amino acids are joined together by one of the hydrogens on the amino group forming water with the OH of the carboxyl group, leaving the nitrogen attached to the carbon of the carboxyl group of the adjacent amino acid (a peptide bond). Amino acids differ in what they have attached to the middle carbon, between the amino and carboxyl groups. The simplest, glycine, just has two hydrogens. The next simplest, alanine has a hydrogen and a methyl group (CH3). The difference between glyphosate and glycine is that the former has a phosphonate group (CH2-PO3H2) attached to the nitrogen. But it still has one hydrogen on the nitrogen so can form a peptide bond with an amino acid. Seneff argues that in protein synthesis the pocket of the enzyme that picks out glycine fits the two hydrogens on the middle carbon of the amino acids and the amino group must be outside this pocket so it can react with a carboxyl group. Glyphosate will therefore fit into this pocket as well as glycine does. But the resulting protein will have a bulky phosphonate group where there should just be a hydrogen. This may result in the protein not folding as it should (in which case it will probably be broken down in the cell) or not performing its function if it does manage to fold.

EPSP synthase usually has a glycine preceded by an alanine at the phosphate binding site that glyphosate disrupts. Seneff argues that because alanine just has a methyl group (CH3) where glycine has a hydrogen there is space for the phosphonate group of glyphosate when it takes the place of glycine during synthesis of EPSP synthase, but that phosphonate group blocks the binding of the phosphate of PEP. In support of this view she points out that organisms which are resistant to glyphosate have an alanine in the position of the critical glycine in EPSP synthase: glyphosate is not able to substitute for alanine in protein synthesis.

Seneff goes on to discuss many other proteins and other molecules where glyphosate may substitute for a critical glycine resulting in disorders in sulphate metabolism, liver disease, decreased sperm production, polycystic ovary syndrome, neurological disorders, chronic fatigue and autoimmune diseases.

This book has a lot of biochemical detail and as a rather rusty biochemist (I studied it to degree level 25 years ago) I could have done with some diagrams showing molecular structures of relevant amino acids and glyphosate, rather than simply their chemical formulae. I am not sure how someone with no biochemical knowledge would cope with it, but I would tell them to persevere for the detailed account it gives of all the mechanisms by which glyphosate may be impacting our health. I have done a lot of thinking about the regulation of chemicals (see my book on this here) and have been most concerned about those chemicals that do not biodegrade but stay around in the ecosystem, accumulating at the top of food chains. Glyphosate can be degraded by some micro-organisms but these tend to be ones that cause us problems, such as cyanobacteria (which cause eutrophication) and Candida, Fusarium and Aspergillus strains of fungi; glyphosate gives them a competitive advantage in providing them with a food source they can use so degradation of glyphosate itself causes problems. We clearly need to be concerned about glyphosate because of the enormous scale of its use. This book makes a compelling case for that use to at the very least be cut back drastically.

However, I do think that sometimes Seneff implies a key role for glyphosate that cannot necessarily be justified. For example, at the end of chapter 1 she suggest that the fact that the US ranks last or next to last among industrialized countries on nearly every health indicator is because it uses more glyphosate per capita than any other industrialized nation: it may be a contributory factor, but surely just one among many.

The weakest chapter is the final one which sets out recommendations for how we should eat to avoid glyphosate and improve our health. This includes some things that are wrong – such as saying that Gabe Brown, one of the leading US regenerative farmers does not use chemicals – he does still use some herbicides (see my review of Gabe Brown’s book Dirt to Soil). And the inclusion in this chapter of things unrelated to the main topic, like suggesting that we should avoid electromagnetic fields, I think weakens the book. While it is understandable that having read this book you would want some advice on what you can do as an individual to reduce your own exposure to glyphosate I would have liked there to be some discussion of the regulatory system that governs use of glyphosate, how that needs to change and how we can influence it to stop glyphosate being used in the first place.

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