Just as DDT was initially hailed as a miracle pesticide and later banned, researchers are beginning to discover serious problems with glyphosate.

- Michael McNeill, Ph.D. quantitative genetics and plant pathology, Iowa State University

Rachel Carson highlighted the dangers of DDT in her groundbreaking 1962 book Silent Spring. Carson used DDT to tell the broader story of the disastrous consequences of the overuse of insecticides, and raised enough concern from her testimony before Congress to trigger the establishment of the Environmental Protection Agency (EPA). Her work attracted outrage from the pesticide industry and others. Her credibility as a scientist was attacked, and she was derided as “hysterical,” despite her fact-based assertions and calm and scholarly demeanor. Following the hearings, President Kennedy convened a committee to review the evidence Carson presented. The committee’s review completely vindicating her findings.

- Pesticide Action Network

Monsanto Roundup (Glyphosate) implicated in Chronic Kidney Disease in Sri Lanka

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Is Monsanto Roundup the new DDT? A recent study published by Channa Jayasumana et al in the March 2014 edition of the Open Access International Journal of Environmental Research and Public Health entitled Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka? offers an explanation for the disease and has resulted in a nation-wide, Sri Lanka ban of Glyphosate, the active ingredient of Roundup – the most dramatic public policy to date. Before delving into the research paper and its implications, however, it’s necessary to have a grounding of the basic biochemistry of glyphosate, the active ingredient found in Roundup.

Introduction to Glyphosate

glyphosate molecule

Glyphosate is the active ingredient of Roundup, the world’s top selling pesticide and one for which Monsanto’s popular line of GMO crops have been engineered to tolerate. Monsanto chemist John E. Franz discovered its herbicide properties in 1970. For anti-GMO activists, GMO foods represent a double dosage of concern:

  1. The Bt-GMO have the gene of a bacteria implanted in it that kills insects as soon as it eats enough of the GMO food. Legally, such bt-GMO is classified as a pesticide and a number of scientists claim that there is lack of evidence showing that such GMO food is safe for human consumption
  2. HT-GMO is more resistant to Roundup and allows more Roundup to be sprayed on it

For years, there have been suspicions that Roundup, and particularly the active ingredient glyphosate are somehow related to a mysterious and fatal kidney disease named CKDu for Chronic Kidney Disease with unknown etiology responsible for the death of tens of thousands of agricultural workers in the agricultural fields of India, Central America and Sri Lanka. Although scientists have not yet found the source, they have suspected it to be due to a combination of factors including chronic dehydration  and exposure to toxins such as pesticides. Glyphosate (N-(phosphonomethyl)glycine) is a biochemical herbicide patented by Monsanto that is used to kill weed (especially annual broadleaf weeds and grasses known to compete with commercial crops) grown around the globe. Technically and biochemically, Glyphosate does this  by disrupting the plants ability to synthesize crucial aromatic plant products such as lignins, alkaloids, flavonoids, benzoic acids, and plant hormones and amino acids needed for protein biosynthesis.

EPSP proteopedia
EPSP synthase is a critical enzyme required to catalyze one of the critical reactions in the seven step Shikimate pathway of plant growth shown in the diagram below in the PEP / EPSP block. Glyphosate disrupts the EPSP synthase process. Glyphosate is a chemical herbicide which kills plants by inhibiting the shikimate pathway. In fact, it is called a competitive inhibitor because it inhibits plant growth by competing with natural molecules for the EPSP synthase.  Glyphosate resembles the transition state that transforms the reactants into products in the reaction that is catalyzed by EPSP synthase. Hence glyphosate (as a transition state analog) binds more tightly to EPSP synthase than its natural substrate and thereby prevents binding of substrate to the enzyme.  In short, glyphosate targets EPSP synthase, the enzyme that catalyzes the conversion of shikimate-3-phosphate and phosphoenolpyruvate into EPSP.

epsp synthase wikipedia
epsp synthase uga edu

Figure 1: Glphosate targets one of the seven steps in the Shikimate pathway: EPSP synthase catalyzes the reaction which converts shikimate-3-phosphate (S3P) plus phosphoenolpyruvate (PEP) to 5-enolpyruvylshikimate-3-phosphate (EPSP).

 

ShikimatePathway-U-of-Nebraska

Figure 2: Shikimate Pathway of Plant Metabolism (Source: University of Nebraska Plant and Soil Science eLibrary)

EPSP Cycle

A great tutorial that shows the natural EPSP cycle in plants and the EPSP cycle disrupted by glyphosate is found here at the University of Nebraska Lincoln site, prepared by Scott Nissen of the Department of Bioagricultural Sciences and Pest Management at Colorado State University and Deana Namuth of the Department of Agronomy and Horticulture at University of Nebraska-Lincoln. The slides below are taken from their animation found at the UNL website. The first series shows the Normal EPSP cycle and the second shows the EPSP cycle disrupted by glyphosate.

Figure 3: Normal EPSP Cycle – hover over slideshow to control speed (Source: University of Nebraska Plant and Soil Science Library)

Figure 4: EPSP Cycle disrupted by glyphosate – hover over slideshow to control speed (Source: University of Nebraska Plant and Soil Science Library)

In the slideshow which illustrates the EPSP synthase catalyst cycle:

  • large red graphic object represents the EPSP synthase enzyme
  • blue rectilineal block – S3P molecule
  • yellow rectilineal block – PEP molecule
  • grey and yellow block – glyphosate molecule

The EPSP synthase enzyme active site binds S3P molecule first. Next, it binds a PEP molecule. When both molecules are bound, this catalyzes a condensation reaction that joins the two into a new molecule. When glyphosates are introduced, it binds with EPSP after S3P has been bound. This blocks PEP from binding and hence prevents the enzyme from catalyzing the condensation reaction between S3P and PEP, stopping an essential step in plant growth.

The Glyphosate binding leads to the inhibition of the enzyme, and consequently shuts down the entire pathway. Since plants require the shikimate pathway to produce aromatic amino acids, this kills the plant. Because animals and humans do not use the shikimate pathway for the synthesis of the aromatic amino acids tyrosine, tryptophan andphenylalanine (instead obtain these amino acids from their diet of organisms like plants which do), this implies that glyphosate play no direct disruptive role in animal and human metabolism.

Glyphosate as a Herbicide

Because of this mode of action, glyphosate is only effective on actively growing plants; not effective as a pre-emergence herbicide. Glyphosate was very rapidly adopted by farmers and when Monsanto introduced glyphosate-resistant crops, it increased sales even further. The glyphosate-resistant crops, also called HT (herbicide resistant) crops, allowed farmers to spray enormous amounts of Roundup on their crop without any adverse effects.

With its heavy use in agriculture, weed resistance to glyphosate was bound to happen if suppliers and farmers did not follow the strict protocols defined by biotechnology scientists. On March 12, 2014, A paper was published in the Proceedings of the National Academy of Sciences entitled Field-evolved resistance by western corn rootworm to multiple Bacillus thuringiensis toxins in transgenic maize which shows disturbing signs that a species of pest called the corn rootworm has grown resistant to Bt-corn.

Glyphosate Chelating Properties

Glyphosate was originally patented as a chelating agent, a compound which binds strongly with metals. The chelating properties of glyphosate have raised concerns with some experts. Iowa-based consultant Michael McNeill is an agronomist with a Ph.D. in quantitative genetics and plant pathology from Iowa State University. His company, Ag Advisory Ltd. advises large-scale corn and soy farmers on weed control and soil fertility. McNeill has worked in the military as a plant pathologist and also managed a Funk Seed research station for 12 years. He has seen firsthand how GMOs and chemicals (especially glyphosate) have affected our land, animals and people. In particuliar, McNeill is familiar with glyphosate as a chelating agent which binds to metal molecules that are valuable to a plant, like iron, calcium, manganese, and zinc.  According to McNeill, the increased use of Roundup is harming crops because it is killing micronutrients in the soil that they need, a development that has been documented in several scientific papers by the nation’s leading experts in the field. He claims that the overuse of glyphosate has resulted in:

  • increase of harmful fungi and parasites like fusarium, phytopthora and pythium
  • decrease of beneficial fungi and other organisms that help plants reduce minerals to a usable state
  • increase of oxidizing agents that create oxides that plants can’t use, leading to lower yields and higher susceptibility to disease

Brief herbicide industry presentation of Roundups chelating (metal binding) properties

Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?

While glyphosate and formulations such as Roundup have been approved by regulatory bodies worldwide and are in wide use, concerns about their effects on humans and the environment persist. Now, in the boldest move to date, Sri Lanka’s president has banned Roundup in Sri Lanka. The president was acting on a research paper released a week earlier by Dr. Channa Sudath Jayasumana, Lecturer of Pharmacology at Faculty of Medicine, Rajarata University in Anuradhapura entitled Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?

Abstract: The current chronic kidney disease epidemic, the major health issue in the rice paddy farming areas in Sri Lanka has been the subject of many scientific and political debates over the last decade. Although there is no agreement among scientists about the etiology of the disease, a majority of them has concluded that this is a toxic nephropathy. None of the hypotheses put forward so far could explain coherently the totality of clinical, biochemical, histopathological findings, and the unique geographical distribution of the disease and its appearance in the mid-1990s. A strong association between the consumption of hard water and the occurrence of this special kidney disease has been observed, but the relationship has not been explained consistently. Here, we have hypothesized the association of using glyphosate, the most widely used herbicide in the disease endemic area and its unique metal chelating properties. The possible role played by glyphosate-metal complexes in this epidemic has not been given any serious consideration by investigators for the last two decades. Furthermore, it may explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America. Although glyphosate alone does not cause an epidemic of chronic kidney disease, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with a localized geo environmental factor (hardness) and nephrotoxic metals.

The Jayasumana study essentially proposes that while glyphosate by itself may not be harmful, when it is exposed to hard water it’s well known chelating effects (ie. binding to metals) can form  glyphosate-metal complexes with a localized geo environmental factor (hardness) and nephrotoxic metals which can toxify the kidney. Jayasumana and his colleagues found a highly significant statistical positive correlation (p<0.008) between number of CKDu patients and water hardness:

jayasumana study figure 1 jayasumana study figure 3

In the paper,  Jayasumana says “The typical half life of the glyphosate was found to be 92 days in water and 47 days in soil [31,32]. However, the absorption of chelating agents or metals has been shown to decrease the biodegradability of glyphosate (Figure 3) [23,27,33–35]. Radioactive 14C-glyphosate studies have shown that half-life can increase up to 7 years [36] or even up to 22 years [37] in the soil (references refer to references in the paper). and “Glyphosate not only forms stable complexes with Ca and Mg, but also with many other divalent and trivalent metallic cations (Figure 4).”

jayasumana study figure 4

In the paper,  Jayasumana says “When we go back to the CKDu situation in Sri Lanka and hypothesize that glyphosate is “Compound X”, we can explain almost all of the above-mentioned observations coherently. It provides rational answers for the geographical distribution of the CKDu and the appearance of the disease in the mid-1990s. Glyphosate and its primary metabolite AMPA can directly leach into the ground water and easily chelate to Ca, Mg and Sr copiously present in ground water in the North Central Province and adjacent rice paddy farming areas in the Sri Lanka. Many farmers use hard water to dissolve glyphosate to prepare the spraying solutions as well. Further it is reported that rice paddy farming soil in CKDu endemic area is rich with Ca, Mg, Fe, Cr, Nickel (Ni), Co and other metals [53,54]. It can easily combine with glyphosate and form complexes, which later leach into the ground water.”

jayasumana study figure 5

Scientist Slams Biotech Industry over Deadly Kidney Disease Epidemic

March 24, 2014 -reprinted in full with permission from Sustainability Pulse

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Dr Channa Jayasumana recently released a study in the International Journal of Environmental Research and Public Health that proposes a link between the world’s number one selling herbicide known as Roundup (aka Glyphosate) and a series of mysterious epidemics of fatal chronic kidney disease of unknown origin (CKDu) affecting several poor farming regions around the world. In Sri Lanka alone CKDu now afflicts 15% of people of working age in the northern part of the country; a total of 400,000 patients with an estimated death toll of around 20,000. Watch the videos “Mystery in the Fields” and “Cycle of Death” for 5 minute documentaries providing additional background information on afflicted areas around the world.

Dr Jayasumana what led you into the investigation of possible links between Glyphosate and CKDu?

In Sri Lanka the disease was first noticed in 1994 at a rice paddy farming colony named Padavi-Sripura and located 350 km North East of the capital city, Colombo. The unique epidemiological feature of the CKDu is commonly known risk factors for CKD such as diabetes mellitus, hypertension and glomerular nephritis is not seen in these patients. Young to middle aged (30 to 50 year old) men with low socio-economic backgrounds are predominantly affected. Epidemiological studies have shown that the disease is related to paddy farming with extensive use of pesticides and chemical fertilizers. The observed geographical and socioeconomic disease patterns led to assumptions that environmental and occupational factors have an important role to play as the main causative agents. Tubulointerstitial disease with negative immunofluorescence for IgG, IgM and complement-3 were more in favour of a toxic nephropathy. However, known nephrotoxins could not coherently explain why CKDu is confined to certain geographical areas of Sri Lanka and why there was no CKDu in Sri Lanka prior to the 1990s. We focused on toxic substances originating from chemical fertilizers and pesticides which were introduced to Sri Lanka in the late 1970s and early 1980s. Earlier, our main concern was arsenic and heavy metals coming from agrochemicals. Nevertheless, comprehensive studies have shown that there could be something else which contributes to the epidemic. When we analysed urine samples of CKDu patients for various organic and inorganic substances, we detected high levels of glyphosate and AMPA apart from arsenic and heavy metals. This led us into the investigation of possible links between Glyphosate and CKDu.

You mention in your study that nephrotoxic metals are found in the water around areas where CKDu is prevalent – could these metals not be the only reason for the chronic kidney disease?

Yes, We have found nephrotoxic metals (arsenic- a metalloid and heavy metals) in drinking water in the CKDu endemic regions. However, the concentrations of these metals are not high. Concentrations of some heavy metals were below the WHO recommended level. Nephrotoxic metals alone are quite unlikely to cause this kind of catastrophic health issue in the region. That is why we assumed that there should be some other molecule that transports and delivers these nephrotoxic metals to the kidneys even when present in low concentrations in drinking water.

What areas of the World are currently affected by CKDu?

11 countries in 3 continents are affected.

  • Sri Lanka – North Central, North Western Eastern and Uva provinces in Sri Lanka
  • India – Andra, Orissa (Odesha) provinces
  • Pacific coast of Central America- El Salvador, Costa Rica, Nicaragua, Honduras, Guatemala and  Southern Mexico.
  • Africa – Egypt, El Minia Governoate, Upper Egypt, Tunisia
  • Vietnam- Mekong river basin

Is it not surprising that with such a high death toll there is not more media coverage of this disease?

This is a disease of poor farmers: a disease of rural villagers in Asian, African and Latin American countries. This is not a disease of the Western World. Hence, a low visibility in print and electronic media. Also there is emerging evidence that the disease is linked to agrochemicals produced by multinationals. They want to hide the link, promote other theories, and undermine the severity of the disease. Leading media institutions in the contemporary world are subverted by the hidden agendas prepared by political and economic behemoths. So how can we expect truthful reporting?

Are you not worried by the possible reaction of the multi-national biotech industry, which produced Glyphosate-based herbicides, to your study?

Our main concern is the innocent farmers in the paddy cultivating areas of Sri Lanka. The CKDu endemic area is the heart of ancient Sinhala-a Buddhist civilisation with two ancient capitals. We have been cultivating rice for two millennia without any problem. All these appeared following the introduction of so-called developed rice varieties and agrochemicals to the region. We are well aware about the reaction of the multi-national biotech industry. We know what happened to the publication by Prof. Gilles-Éric Séralini. We are ready to face them.

What qualities does Glyphosate have which could make it into a killer of so many people? Is Glyphosate alone the reason for the outbreak of CKDu?

The strong metal chelating property of glyphosate is the key factor. Glyphosate was first patented as a chelating agent, wetting agent and biologically active compound. It was initially used as a descaling agent to clean out calcium and other mineral deposits in pipes and boilers of residential and commercial hot water systems. Descaling agents are effective metal binders, which grab on to Calcium, Magnesium and heavy metals to make the metal water soluble and easily removable. Later, Monsanto acquired the chemical and obtained a patent for its herbicidal properties. Once glyphosate is combined with a metal, it does not follow the normal degradation pathway and remains in the environment or biological systems for a long time. Glyphosate alone is a weak nephrotoxic substance. When it combines with arsenic or heavy metal, its nephrotoxic property is enhanced a thousand times. Glyphosate alone is not the cause for CKDu but, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with nephrotoxic metals.

Sri Lanka has now become the first country to officially ban all Glyphosate-based herbicides after an order from the Sri Lankan President. Should other countries follow Sri Lanka in banning Glyphosate herbicides based on your study findings?

We just published the hypothesis. We had to find a journal, which would publish our hypothesis with a detailed explanation amounting to more than 9900 words. Now we are in the process of publishing experimental data. There is significant contamination of the environment and biological systems with Glyphosate-Metal complex. At the same time, the disease is spreading rapidly throughout the farming areas. We found the cause and solution to the CKDu by re-discovering our own unique knowledge system. The cultivation technology that we advocate was in existence during the ancient civilisation and reformulated by us. The yield of traditional rice varieties cultivated without agrochemicals but using indigenous technology has cost savings for farmers even after considering fertilizer subsidies. HE the president of Sri Lanka was brave and intelligent enough to take immediate actions to protect his people. Political authorities in other countries with similar epidemics have the option to follow Sri Lanka or keep silent and bow down to multinationals and watch helplessly till their once proud civilisations wither away.

Dealing with CKDu

Countries with CKDu are meeting to share knowledge and work towards a common solution to the problem:

Sri Lanka and El Salvador meeting and collaboration to discuss how to deal with CKDu