A Pesticide as Medicine? Medicine as Poison? Or What is in a Name? 3

The Type III (or Type IV) ranking of glyphosate was long ignored by the anti-biotech opponents of Ht cotton as was the assessment by WHO and various Cancer societies that it was not likely a carcinogen. Suddenly with the new findings, the same groups are now demanding policy actions based on the findings of a source which they long implicitly discredited by ignoring it. Any credible evidence that does not support their firmly held beliefs does not exist in their universe. Nor did they indicate any awareness of the array of more toxic pesticides that were replaced by glyphosate or the resulting significant improvement in the Environmental Impact Quotient (EIQ – “The EIQ impact assessment is based on the three principal components of agricultural production systems: a farm worker component, a consumer component, and an ecological component.”) and other measures of toxicity and environmental impact. (A Method to Measure the Environmental Impact of Pesticides – http://www.nysipm.cornell.edu/publications/eiq/ and
http://cars.uark.edu/ourwork/Cotton%20Toxicity%20Final%20Report%203.3.10%20Project%2009-591.pdf, Glyphosate and Cancer and Why It’s Still Recommended for Weed Control – http://hyg.ipm.illinois.edu/article.php?id=657).
In March 2015, the World Health Organization’s International Agency for Research on Cancer (IARC) convened 17 scientists from 11 countries to evaluate existing science on five pesticides, including glyphosate. The group deemed glyphosate “probably carcinogenic,” the second-highest designation given out by IARC behind “carcinogenic to humans.”  (https://news.vice.com/article/the-most-widely-used-herbicide-in-the-united-states-could-cause-cancer-in-humans-says-a-world-health-organization-study  see also   IARC Monographs Volume 112: evaluation of five organophosphate insecticides and herbicides – http://www.iarc.fr/en/media-centre/iarcnews/pdf/MonographVolume112.pdf  and Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate – http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70134-8/fulltext  ) –This previously non-existent evaluation was suddenly noticed and its alleged conclusions spread at warp speed throughout the NGO even though the final report was not due out until July 2015.

As would be expected, those who leaped on the initial report either did not read beyond the headlines or simply over-interpreted it to suit their ideological needs. The initial brief for glyphosate clearly distinguished between consumer use where there was no change from the previous conclusion of not being a hazard at the dosages encountered and occupational use, primarily in agriculture where there was a potential hazard  but a risk factor was not given.  It is important to note, that there were no new studies or data, just a re-evaluation of existing studies. It is understandable then that a number of regulatory agencies in U.S. and Europe quickly re-affirmed, in some case strongly re-affirmed their previous determination as to the safety of glyphosate.

One of the worst distortions of the report was on VICE an HBO presentation that was offered as a balanced look at GMOs. The host of the program, Isobel Yeung interviewed critics of GMOs clearly with the questions that they wanted asked while aggressively questioning a distinguished scientist (and Monsanto vice-president) on a rather trivial point that she did not seem to understand.  The program was unbalanced throughout (Savior Seeds: VICE on HBO Debrief (Episode 31) Isobel Yeung, https://www.youtube.com/watch?v=aLYbnfz3OU4 –Unfortunately, the full program is available only to subscribers).

Towards the end of her program, there are two brief snippets from an interview with Dr. John McLaughlin a member of the IARC committee that made the re-assessment of the toxicity of glyphosate and other chemicals. The snippets were either a case of creative editing – the video equivalent of cherry-picking – or extreme cleverness in asking questions that would only get the answers she sought.
Fortunately, Dr. McLaughlin was on a long program with another scientist where the interviews were not edited (The Agenda with Steve Paikin: The Last Roundup Debate – http://tvo.org/video/212783/last-roundup-debate). He distinguished between hazard and risk and indicated that as a hazard, the new assessment was a worst case scenario and not a risk factor. Even for agriculture, the major potential occupational hazard, “McLaughlin says that if the glyphosate is used according to instructions given by Health Canada, it is not a health risk” (Video: Canadian scientists say glyphosate hazard but not health risk – http://www.geneticliteracyproject.org/2015/04/29/video-canadian-scientists-say-glyphosate-hazard-but-not-health-risk/  ).

Agroecology is currently the rage among activists in developed countries simultaneously increasing yields and protecting the crop against pests of all kinds. It needs to be stated that all agriculturalists are agroecologists in that they recognize the agriculture takes place in differing environments which must be understood if one is to be successful in producing a crop and sustaining production through time. It is not a perspective invented by and unique to urban activists in developed countries who have never in out in the field and had to deal with real problems of producing a crop.

It is easy for a representative from Consumer’s Union on a panel in Manhattan to proclaim “We favor a knowledge-based approach rather than a chemical-based approach to increasing production” without having to identify and implement these “knowledge-based’ solutions. Walter De Jong, a Cornell University agriculturalist on the same panel “was shocked at how people who don’t live near farms feel entitled to advise farmers, especially on environmental matters.” He adds that “There is a romantic notion of environmentalism, and then there is actual environmentalism.” In addition, “farmers are very conscious of the environment. They want to hand off their operation to their kids and their kids’ kids, so they maintain the land the best they can while doing what they need to do in order to sell their harvest,” (Contemporary Selective Breeding. Plant Edition. http://fafdl.org/blog/2015/06/06/contemporary-selective-breeding-plant-edition/, see also  The Return of a Simplot Conspiracy – http://www.cc.com/video-clips/ixxwbt/the-daily-show-with-jon-stewart-the-return-of-a-simplot-conspiracy ).
No one would deny that an intensive study of agroecology as a scientific inquiry and discipline could yield many insights and make a substantive contribution to agricultural development throughout the world. The problem is that it has become a religion and not a science and is being offered in exclusion to other approach and not complementary to them. The larger problem is that as such, they don’t work except in the minds of urban activists mentally and physically divorced from the realities of agriculture.

Nathanael Johnson asks the question – “Why aren’t  agroecological techniques farming spreading faster among poor farmers?” Johnson proceeds to list the many virtues of agroecology. Children in school and in 4H clubs are taught agroecology and organic methods. This has been going on for decades yet when they become adults and actually farm, they use pesticides. “It could be that organic methods just aren’t working for poor farmers”(Even this organic advocate thinks African farmers need herbicide by Nathanael Johnson – http://grist.org/food/even-this-organic-advocate-thinks-african-farmers-need-herbicide/ ).

A title of paper by a dedicated scientist is revealing – “Facing food insecurity in Africa: Why, after 30 years of work in organic agriculture, I am promoting the use of synthetic fertilizers and herbicides in small-scale staple crop production” by Don Lotter.

“Food insecurity and the loss of soil nutrients and productive capacity in Africa are serious problems in light of the rapidly growing African population. In semi-arid central Tanzania currently practiced traditional crop production systems are no longer adaptive. Organic crop production methods alone, while having the capacity to enable food security, are not feasible for these small-scale farmers because of the extra land, skill, resources, and 5–7 years needed to benefit from them—particularly for maize”

Lotter further argues “Conservation Agriculture (CA) in Africa has two main categories—organic and herbicide-mediated. The organic version of CA, despite years of promotion, has had a low rate of adoption. Herbicide-mediated zero tillage CA via backpack sprayer can substantially increase conventional maize yields while at the same time nearly eliminating erosion and increasing rainwater capture up to fivefold.”

And the pesticide that he advocates is Glyphosate a herbicide “which is a non-proprietary product produced in Africa and approved for small farm use. The systemic nature of glyphosate allows the killing of perennial grasses that would otherwise need deep plowing to kill. The rooted weed residues protect the soil from erosion. The risks of glyphosate use are substantially outweighed by the benefits of increased food security and crop system sustainability” (Agriculture and Human Values March 2015, Volume 32, Issue 1, pp 111-118 , http://link.springer.com/article/10.1007%2Fs10460-014-9547-x).

They don’t work is a refrain I and others have often heard in the developing world.

After World War II, antibiotics and pesticides such as DDT seemed like miracles saving lives and crops and killing disease vector insects such as malaria bearing mosquitoes. They were cheap and effective. We quickly learned how to use them but unfortunately, we did not at first know when not to use them. This could only be learned by making mistakes of overusing them.

In many parts of the developing world, modern synthetic pesticides came in the 1960s with the Green Revolution. For those for whom losing a crop to disease or insects was a constant threat, pesticides had the same status as antibiotics and vaccines that also saved human lives.

The time to spray again was defined by the calendar and not by objective conditions in the field. In the 1970s and beyond, when various IPM programs emerged to facilitate using less pesticide and using them more effectively, the task became one of convincing the farmer. To the farmer who as a child or young adult experienced the devastating effect of a crop lost, convincing them to use less pesticide was not an easy sell.

A story that I have often told was about interviewing a farmer about his use of pesticides in growing cabbages. I asked him what would he say if I told him that a farmer across the valley harvested the same size crop that he did but used less than half the pesticide that he did. He very calmly and politely replied that he would not believe me.

The following articles and the quotes from them might make some interesting reading for those who remain adamant that it is beyond the realm of belief that a pesticide could be anything other than a POISON.

Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis by Li Q, Lambrechts MJ, Zhang Q, Liu S, Ge D, Yin R, Xi M, You Z, Journal of Drug Design, Development and Therapy, Vol. 7, July 24, 2013, pp. 635-643

“This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC89043/

Antimicrobial Agents Chemotherapy, Vol.43, No. 1, January 1999, Pp. 175–177.

Targeting the Shikimate Pathway in the Malaria Parasite Plasmodium falciparum By Glenn A. McConkey. Antimicrobial Agents Chemotherapy, Vol.43, No. 1, January 1999, Pp.175–177.

“The sensitivity to shikimate analogs suggests that the shikimate pathway is viable for malaria chemotherapy. The 50% inhibitory concentrations of these analogs are below those of some currently used antimalarial drugs (13). … Therefore, shikimate analogs may act as universal inhibitors of apicomplexan parasites, such as Toxoplasma gondii and Cryptosporidium parvum, which cause opportunistic infections in patients with AIDS.”

“Based on the observations that mice were protected by 6-fluoro-shikimate from intraperitoneal bacterial infection (2) and that mice were cleared of Toxoplasma by treatment with a glyphosate-pyrimethamine formulation (13), the effectiveness of 6-fluoro-shikimate on malaria treatment awaits testing in rodent models.”

Evidence for the shikimate pathway in apicomplexan parasites by Fiona Roberts1,2,3, Craig W. Roberts1,2,3,4, Jennifer J. Johnson3, Dennis E. Kyle5, Tino Krell6, John R. Coggins6, Graham H. Coombs6    Nature,  Volume 393 Number 6687, June 25, 1998, pp 801-805.

“The discovery of the shikimate pathway in apicomplexan parasites provides new opportunities for the development of antimicrobial agents effective against these parasites. The inhibitor used in these studies, glyphosate, should be a valuable lead compound in this process. A variety of derivatives of glyphosate are currently being used to elucidate structure–function relationships for inhibitors of plant EPSP synthases18, and a similar approach could be useful for characterizing the active site of the parasite enzymes. Inhibitors of chorismate synthase19 and other enzymes within the shikimate pathway also are being developed in the search for new herbicides and antimicrobial agents effective against bacterial and fungal pathogens. These too may be useful against apicomplexan parasites. Indeed, because many other microbes that cause opportunistic infections of AIDS patients, including Pneumocystis carinii20 and Mycobacterium tuberculosis21, also have the shikimate pathway, there is now the exciting possibility that compounds with broad-spectrum activity could be useful against several opportunistic pathogens “

Could malaria be killed by a garden weedkiller? by Helen Phillips, Nature News, Volume 394, Number 6688, July 2, 1998, doi:10.1038/news980702-2.

“The parasites that cause malaria, toxoplasmosis and cryptosporidiosis are all members of a group of microorganisms known as the Apicomplexa. This group of parasites kills well over one million people each year, and includes some of the most common opportunistic infections of AIDS patients. New medicines to treat these infections are needed urgently.

“In the 25 June 1998 issue of Nature one team of researchers describe how they are well on the way to finding such a treatment. The downfall of the Apicomplexa might turn out to be a common herbicide.

“A herbicide may sound like a strange treatment for a parasitic microorganism. But plants and many microorganisms share a common biochemical pathway that other living forms – notably humans – don’t have. An agent that disables this pathway will kill plants and microorganisms, but will be completely harmless to humans.

……..

“The researchers conclude that ‘such combinations should be useful for the treatment of toxoplasmosis. Furthermore, they could also have applications against other diseases caused by apicomplexan parasites, such as malaria.”
THE SHIKIMATE PATHWAY by Klaus M. Herrmann and Lisa M. Weaver, Annual Review of Plant Physiology and Plant Molecular Biology, Vol. 50, June 1999, pp. 473-503.

Source

Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907; e-mail: Herrmann@biochem.purdue.edu, Monsanto Company, St. Louis, Missouri 63198; e-mail: Lisa.m.weaver@monsanto.com
Abstract

“The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants. “

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