Glyphosate: Some Science

A 'round up' of what we really know

Glyphosate is the main ingredient of a class of herbicides used worldwide in eye-watering quantities. But what else about glyphosate makes your eyes water? Why is glyphosate high on the list of substances under scrutiny by the new US Secretary of State for Health and Human Services.

Take a look at the structure of glyphosate below. Copied from a recent review of glyphosate and human health.

Those of you with a scientific bent will immediately recognise the similarity with the essential amino acid glycine.

But and it is a very important ‘but’ this is where any chemical similarity ends. Regardless of the fantasies of some whom clearly believe their own pseudoscience, glyphosate cannot and does not substitute for glycine in any known biochemical pathway.

Further anomalies in the ‘published’ scientific literature refer to glyphosate as a chelator. Indeed this was once considered part of its action as a potent herbicide. However, research does not support this mechanism, for example glyphosate cannot form stable complexes with metals in plant phloem. Again, fantasists have written ad nauseum about how glyphosate binds metals in human tissues resulting in all manner of toxicity.

I am not completing dismissing a role for glyphosate in metal binding. I am simply pointing out that in biologically relevant milieu whether in plant or human glyphosate cannot form stable metal complexes. However, allow me one proviso. Most of you will know what is coming next. Yes, in the highly acidic environment of the human gut glyphosate will complex aluminium. In theory at least glyphosate could facilitate the absorption of aluminium across the gastrointestinal tract by delaying the precipitation of aluminium in the small intestine. Just perhaps there are other environments including those pertinent to glyphosate’s activity as a herbicide where complexation of aluminium is possible.

So, why is glyphosate used as a herbicide. It must be toxic, mustn’t it?

We are informed that the toxicity of glyphosate is through its inhibition of the Shikimate pathway and hence the biosynthesis of aromatic amino acids in plants. I am aware of only one high profile scientific paper that supports the purported mode of toxicity of glyphosate. That is the incorporation of glyphosate into the structure of the protein abbreviated as EPSPS in the above schematic. As scientists we have to believe that by pure chance EPSPS accommodates the full structure of glyphosate and in so doing stops the Shikimate pathway. Well how lucky we are that glyphosate (or perhaps something very similar) was not present on Earth during the evolution of plants (and some microorganisms). Life on Earth would be very different in such circumstances!

Let me be just a little bold. Really unusual for me I know. I don’t believe this mechanism of toxicity of glyphosate in plants. Instead, take a look at the step prior to the one involving glyphosate. An enzyme known as a kinase adds a phosphate group to Shikimic acid to form Shikimic acid 3-phosphate. A phosphorylation reaction involving Mg-ATP. Now stop for one moment and recall what is the most potent inhibitor of protein kinases. Yes, that is right Al-ATP! If aluminium inhibits the activity of Shikimate kinase then the Shikimate pathway is stopped, biosynthesis of aromatic amino acids is prevented and the plant dies.

Why not finish with one last blockbuster.

Pure glyphosate is not toxic to plants. Monsanto knows this, most informed scientists in this field (no pun intended) know this. Hence it is Round Up or similar glyphosate-containing herbicide that is toxic. These herbicides include many other components some of which are on the label. They certainly include adjuvants that help substances such as glyphosate penetrate the leaf surface. What if they also include aluminium such that when glyphosate enters a leaf it also facilitates the entry of aluminium. The glyphosate-aluminium complex will not be stable upon its entry into phloem and so aluminium will be released to potentially stop the Shikimate pathway through inhibition of Shikimate kinase. Now, does that seem more plausible to you than the one in hundreds of million chance of glyphosate incorporating into the structure of EPSPS?

Secretary Kennedy, time to get on the phone to Administrator Zeldin at the EPA and commission some science. The hypotheses expounded above are eminently testable and may help to put to bed all the fantasists and fantasies surrounding glyphosate.