"Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases" by Anthony Samsel and Stephanie Seneff.
I could have sworn I saw an entry on Samsel's and Seneff's "paper" on glyphosate toxicity (http://www.mdpi.com/1099-4300/15/4/1416) somewhere here on BioFortified already. If not, then I'd like to initiate this thread to debunk at least a tiny fraction of all the outrageous claims in their 48-page paper. Please feel free to join in!
I've already had several people referring to this "review" on Keith Kloor's blog as well as a couple of facebook pages. There are already a couple of obvious criticisms from the start such as:
(1) the fact that neither author appears to have any biological or medical credentials
(2) the fact that this is a review and not an original research article
(3) the fact "Entropy" is a low-impact journal of thermodynamics, information theory, artificial intelligence - NOT toxicology or epidemiology! According to the Entropy "Aims and scope" page (http://www.mdpi.com/journal/entropy/about) the listed subject areas are:
- general aspects of entropy and information concepts as used in statistical mechanics, thermodynamics, etc.
- the second law of thermodynamics
- information theory
- system theory and cybernetics
- artificial intelligence, neural networks, complex systems, man-machine interfaces, self-organization theories, systems therapy
- pattern recognition
- chaos, complexity, self-organization, symmetry breaking, stability, reversibility and spontaneity
- quantitative relations of entropy (information loss) and other concepts (e.g., symmetry, similarity, orderliness, simplicity and complexity)
- molecular evolution, biological evolution and the evolution of the universe
- application of entropy and information studies in any natural and social sciences
I'd like to kick things off with this little nugget of a sentence from page 5 of their review:
"Pseudomonas spp. is an opportunistic pathogen and an antibiotic-resistant Gram-negative bacterium that has been shown to be able to break down glyphosate to produce usable phosphate and carbon for amino acid synthesis, but a toxic by-product of the reaction is formaldehyde , which is neurotoxic, and low levels of formaldehyde can induce amyloid-like misfolding of tau protein in neurons, forming protein aggregates similar to those observed in association with Alzheimer's disease ."
The two references cited by S & S are:
37. Shinabarger, D.L.; Braymer, H.D. Glyphosate catabolism by Pseudomonas sp. strain PG2982. J. Bacteriol. 1986 , 168, 702–707. (freely available here http://jb.asm.org/content/168/2/702.full.pdf)
38. Nie, C.L.; Wang, X.S.; Liu, Y.; Perrett, S.; He, R.Q. Amyloid-like aggregates of neuronal tau induced by formaldehyde promote apoptosis of neuronal cells. BMC Neurosci. 2007, 8, 9. (freely available here http://www.biomedcentral.com/1471-2202/8/9/)
Ok. This sentence contains two main statements. (1) Pseudomonas bacteria produce formaldehyde as a byproduct of glyphosate catabolism. (2) Formaldehyde can induce tau protein aggregation in neurons reminiscent of Alzheimer's disease. Both statements are true. But when you put them together in the same sentence, the authors are implying that glyphosate catabolism by soil-living Pseudomonas bacteria cause toxic formaldehyde emissions that may cause Alzheimer's disease in farmers or others in the vicinity of a glyphosate-sprayed field. They don't spell it out but you can bet that the non-specialist reader will. Now that would require some serious long-term safety studies, eh?
As it happens my field of expertise is microbial metabolism, which is why this sentence stood out. Let's have a closer look at just how Pseudomanas degrades glyphosate. According to the cited paper by Shinaberger & Braymer, Pseodomonas sp. PG2982 first cleaves the C-P bond of glyphosate producing phosphate and sarcosine - also known as N-methylglycine. This reaction is carried out by the enzyme C-P lyase, which was eventually cloned by Selvapandiyan and Bhatnagar (http://link.springer.com/article/10.1007/BF01577437). The phosphate group gets assimilated as-is. That leaves the sarcosine molecule. If you demethylate its amine group you get glycine, which is one the 20 standard amino acids common to all living organisms. If necessary, glycine can be further metabolized to give glyoxylate (which can be assimilated as a carbon source) and ammonia (which is the starting point for nitrogen assimilation). This is where formaldehyde (HCHO) enters the picture. The enzyme that demethylates sarcosine to produce glycine is called sarcosine oxidase (http://www.ncbi.nlm.nih.gov/pubmed/15922624). The methyl group (CH3) which is removed from the amine group of sarcosine gets converted into formaldehyde. So there's the formaldehyde ready to give you Alzheimer's! But it doesn't end there. Formaldehyde is a very reactive molecule and therefore very toxic. A Pseudomonas bacterium chewing away on glyphosate would die very quickly if it allowed the concentration of formaldehyde to build up. So what does it do? Turns out that Pseudomonas bacteria have ways to detoxify formaldehyde (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687156/). The majority of cells (bacterial, animal etc) will convert formaldehyde to the much less toxic formic acid (HCOOH). Formic acid can then either be turned into carbon dioxide (which is what our cells do) or assimilated as a source of carbon or energy (which is what many microbes do).
So, a field newly sprayed with glyphosate will NOT emit any significant amounts of formaldehyde. And even if it did, the formaldehyde molecule is so reactive that it would react with other compounds in the soil and not escape into the air.
End of story? Not quite. Here's the final point that emphasizes the intellectual dishonesty of that single sentence in the S & S paper - HUMAN CELLS ALSO PRODUCE FORMALDEHYDE BY DEMETHYLATING SARCOSINE INTO GLYCINE USING THE SAME ENZYME! (http://en.wikipedia.org/wiki/Sarcosine_dehydrogenase) That's right. Our own cells are producing formaldehyde constantly. So why haven't we all got Alzheimer's yet? Because, just like Pseudomonas, our cells are able to detoxify formaldehyde. First the formaldehyde molecule reacts spontaneously with glutathione to produce S-formylglutathione. The enzyme S-formylglutathione hydrolase then cleaves off the former formaldehyde molecule but now in the form of formic acid. Finally formate dehydrogenase converts the formic acid into carbon dioxide and that's it.
So much disinformation in one pesky little sentence and so much specialist knowledge required to debunk it. Imagine how much there must be in the entire thing...