Saturday, July 26, 2014

Pesticide Linked to 3 Generations of Disease: Methoxychlor Causes Epigenetic Changes

Washington State University researchers say ancestral exposures to the pesticide methoxychlor may lead to adult onset kidney disease, ovarian disease and obesity in future generations.
“What your great-grandmother was exposed to during pregnancy, like the pesticide methoxychlor, may promote a dramatic increase in your susceptibility to develop disease, and you will pass this on to your grandchildren in the absence of any continued exposures,” says Michael Skinner, WSU professor and founder of its Center for Reproductive Biology.
He and his colleagues document their findings in a paper published online in PLOS ONE. The study was funded by the National Institutes of Health.
DDT replacement banned in 2003
Methoxychlor—also known as Chemform, Methoxo, Metox or Moxie—was introduced in 1948 and widely used during the 1970s as a safer replacement for DDT. It was used on crops, ornamental plants, livestock and pets. It is still used in many countries around the world.
It was banned in the U.S. in 2003 due to its toxicity and ability to disrupt endocrine systems. Methoxychlor can behave like the hormone estrogen and profoundly affects the reproductive system.
Supports earlier epigenetic findings
When Skinner and his colleagues exposed gestating rats to methoxychlor at a range typical of high environmental exposures, they saw increases in the incidence of kidney disease, ovary disease and obesity in offspring spanning three generations. The incidence of multiple diseases increased in the third generation or “great-grandchildren.”
The researchers say the pesticide may be affecting how genes are turned on and off in the progeny of an exposed animal, even though its DNA and gene sequences remain unchanged.
This is called transgenerational epigenetic inheritance. In recent years, the Skinner lab has documented epigenetic effects from a host of environmental toxicants, including DDT, plastics, pesticides, fungicides, dioxins, hydrocarbons and the plasticizer bisphenol-A or BPA. The newest findings support those observations.
Implications for obesity, fertility, disease
The work is also the first to show that a majority of transgenerational disease traits can be transmitted primarily through the female line.
Additionally, the study identified mutations in the sperm epigenome of great-grandchild male rats. The epigenome functions like a set of switches for regulating gene expression and can be altered by environmental conditions.
The epigenetic changes observed were specific to methoxychlor exposure and may prove to be valuable biomarkers for future research on transgenerational disease.
For people exposed to the pesticide, Skinner says his findings have implications such as reduced fertility, increased adult onset disease and the potential to pass on those conditions to subsequent generations.
He suggests that ancestral exposures to methoxychlor over the past 50 years in North America may play a part in today’s increasing rates of obesity and disease.
 BY FRACTURED PARADIGM – JULY 25, 2014 POSTED IN: PESTICIDES & HERBICIDES  

Read more: Pesticide Linked to 3 Generations of Disease: Methoxychlor Causes Epigenetic Changes http://fracturedparadigm.com/2014/07/25/pesticide-linked-to-3-generations-of-disease-methoxychlor-causes-epigenetic-changes/#ixzz38eovBJgu

US Experts Push Congress to Reject Toxic Herbicide Mix ‘Enlist Duo’

Prominent doctors, scientists and business leaders today urged Congress to pressure the Obama administration to reject an application to market “Enlist DuoTM,” a new toxic herbicide mix of 2,4-D and glyphosate.
enlist duo
The Environmental Protection Agency is currently reviewing an application from Dow AgroSciences, a wholly owned subsidiary of Dow Chemical Co., to sell Enlist Duo for use in agriculture. Enlist Duo would be used on millions of acres of farm fields in combination with a new type of herbicide-resistant, genetically engineered crops.
The medical and scientific experts told a Congressional briefing that this would put human and environmental health at risk.
The U.S. Department of Agriculture is weighing a separate application from Dow to market corn and soybean seeds that the company genetically engineered to tolerate the 2,4-D/glyphosate combination.
Those who spoke at the briefing to oppose Dow’s application included Dr. Philip Landrigan of Mount Sinai School of Medicine, Dr. Catherine Thomasson of Physicians for Social Responsibility, John P. Wargo, Ph.D. of Yale University, Doug Gurian-Sherman, Ph.D. of Center for Food Safety and Gary Hirshberg of Stonyfield Farm and the advocacy group Just Label It.
“Exposures to herbicides in early life can lead to disease in childhood or disease later on in adult life or even old age,” said Dr. Landrigan, dean for global health at Mount Sinai School of Medicine. “Herbicide chemicals can also cross from mother to child during pregnancy and prenatal exposures that occur during the nine months of pregnancy are especially dangerous.”
“Physicians are very concerned about exposure to the combination of 2,4-D and glyphosate because of the potential lifelong and irreversible effects on the health of vulnerable populations, including children, pregnant women and farm workers,” said Dr. Thomasson, executive director of Physicians for Social Responsibility. “Policy decisions should take into account the costs that can result from failure to act on the available data on toxic herbicides.”
Americans are already exposed to 2,4-D in herbicides applied to lawns, turf grass and other non-agricultural sites. Exposure to the toxic defoliant has been linked to non-Hodgkin lymphoma and Parkinson’s disease as well as immune system, thyroid and reproductive problems. Glyphosate is the harmful active ingredient in Roundup, the infamous weed killer developed by chemical giant Monsanto.
“2,4-D already is permitted by EPA to remain as residues on over 300 different forms of food,” said John P. Wargo, Ph.D., professor of environmental health and politics at Yale University. “Spraying millions of additional acres with these chemicals will increase their contamination of soils, surface and groundwater and foods bearing their residues. If applied by aircraft, sprays will drift to adjacent lands, potentially endangering those who reside, go to school or work nearby.”
Crops genetically engineered to withstand Roundup were introduced in the mid-90s. As scientists predicted, weeds quickly developed resistance to the herbicide, which in turn led to the use of hundreds of millions more pounds of the weed killer than would have occurred without these crops.
“The toxic herbicide mix is being proposed because glyphosate alone is no longer working, since its overuse has led to the development of herbicide-resistant ‘superweeds’,” said Gary Hirshberg, chairman of Stonyfield Farm and Just Label It. “This ‘chemical treadmill’ benefits the GE patent holders at the expense of farmers, human health and the environment.”
“The biotech industry is about to repeat the same mistakes that got us into this predicament,” said Doug Gurian Sherman, Ph.D, senior scientist with Center for Food Safety. “The public must demand policies and research that help farmers adopt proven, ecologically-based farming systems with minimal pesticide use that are productive, profitable and better for society.”
In June, 35 doctors, scientists and researchers, including Dr. Chensheng (Alex) Lu of Harvard School of Public Health and Dr. Raymond Richard Neutra, a retired division chief of the California Department of Public Health, sent a letter to EPA Administrator Gina McCarthy urging her to deny Dow’s application.
Before the public comment period ended, EPA received half a million comments opposing the controversial proposal.
“The risks of approving a new 2,4-D mixture are clear,” said Mary Ellen Kustin, senior policy analyst at the Environmental Working Group. “If approved, the use of 2,4-D would increase three-to-sevenfold by 2020, according to the USDA. The risks are too great and benefits too few to jeopardize public health and the environment.”

Dioxin So Bad USA and NZ Pretend No Problem

Seventy-five different Dioxins have been identified, each with its own chemical structure and a unique toxicity.[4] Large groups of related compounds such as polycholorinated biphenyls (PCB) and dibenso furans, have similar affects. Several of these dioxins in various amounts were present within the various herbicides sprayed in Vietnam. The worst and most toxic dioxin, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (abbreviated as TCDD), was a chemical contaminant found in over 11 Million gallons of Agent Orange. The supposed trace amounts of TCDD are estimated at 170 kilograms and represents the largest dioxin release in history.[4] Environmental Protection Agency in its recently completed re-evaluation of its 1994 report on Dioxin, reported data that strongly supports the dangers of dioxin yet it stopped short of initiating or banning products containing dioxin.[12] This work did suggest the potential for a very high risk in the general population if it occurred on the order of 1 in 10,000 to 1 in 1000.[12,34,52]
http://vvi.org/Content/mjournal.asp

Photo: The Agent Orange manufactured by Monsanto contained 2,3,7,8-tetrachlordibenzo-para-dioxin (TCDD), extremely deadly even when measured against other dioxins. The levels found in domestic 2,4,5-T were around 0.05 ppm, that shipped to Vietnam peaked at 50 ppm, ie 1,000 times higher than the norm. ( NORM???? or considered a safe level...?)

#monsanto #dow #maui #hawaii #biotech #molokai

http://www.whale.to/a/monsanto_h.html
The Agent Orange manufactured by Monsanto contained 2,3,7,8-tetrachlordibenzo-para-dioxin (TCDD), extremely deadly even when measured against other dioxins. The levels found in domestic 2,4,5-T were around 0.05 ppm, that shipped to Vietnam peaked at 50 ppm, ie 1,000 times higher than the norm. ( NORM???? or considered a safe level...?)
http://www.whale.to/a/monsanto_h.html

Kimberly Usher's photo.
"In Vietnam they have found levels of 30 to 108 parts per trillion in blood," he said. "Levels in Maori women around the Bay of Plenty, where the herbicide was extensively sprayed, have already been found to be up around 26.7ppt. As of yet we still don’t know what the blood levels are in New Plymouth."

Gibbs says even burning the waste didn’t destroy it. Instead waste streams left residue in the soil, on washing hanging out to dry and on barbecues. "We ate it, breathed it and wore it. When the Yanks burnt it off after Vietnam they burnt it off 80-90 miles down wind from Johnson Island.

"We burnt ours downwind on the whole town of New Plymouth. In the 1987 enquiry they said they found no evidence of dioxin in people or soil. But what they had was a 1,500 ppt safe level. The highest recorded in Vietnam was 808 ppt. In New Plymouth we’ve already levels up to 310 ppt." His views may be ignored by health officials in New Zealand, but they have found credence in America. George Lucier, director of the National Toxicology Programme, and author of the Environmental Protection Agency report, says there is no avoiding dioxin.

"Even penguins in Antarctica have dioxin in them. No-one sets out purposely to make dioxin. It is an unwanted side-product that you get from burning. Anytime you combine heat, chlorine and organic material, there is the possibility of making dioxins."

Lucier says scientists did not quite understand how dioxin damaged the body, but did know it acted on a universal mechanism controlling cell functions.

Dioxin attaches, or binds tightly, to the AII receptor - a kind of cellular doorway found in virtually all cells in the body. Once there, it changes the function of hundreds of genes. It will either stimulate gene expression of suppress it.

Dioxin exposure has been linked to many different tumours, especially non-Hodgkin’s lymphoma, respiratory cancers, soft tissue sarcoma and prostate cancer. One Italian study of dioxin in children found hormonal changes.

"When they have children, most or all their kids are girls, not boys," says Lucier. "Dioxin affects pathways that are involved in normal growth and differentiation, so it can cause birth defects," he adds. "It can effect sperm counts."

Drake thought the new Labour government, with its Green allies, would order a fresh enquiry following new American evidence on the damaging effects of dioxin. Instead, he says, they are happy to sweep the issue under the carpet. In June of this year Health Minister Annette King refused calls for a new enquiry, relying on conclusions found in 1986 – interestingly a report delivered under the previous Labour Government."

The enquiry team concluded that there was no evidence of major contamination in New Plymouth or of any major health risk Yet residents say that part of the information used in that research was based on American studies which have since found to be fraudulent. This is where the issue becomes more complicated. In 1949 an explosion at the Monsanto chemical plant in Nitro, West Virginia, exposed many workers to effects of 2,4,5-T. Thirty years later Monsanto scientists and an independent researcher, Dr Raymond Sunkind, compared death rates amongst workers exposed to 2,4,5-T to those who hadn’t been exposed. When no differences between the two groups were found, Monsanto claimed that dioxin did not cause cancer. Evidence of inaccuracies were only exposed in the late 1980s when a group of Missouri citizens sued Monsanto for alleged injuries suffered during a chemical spill caused by a train derailment in 1979. While reviewing documents obtained from Monsanto, it was held in court that during the early studies, scientists omitted five deaths from the dioxin-exposed and put them in the unexposed group. Given that, and the leaked report to the Washington Post, it’s small wonder that the residents are now calling for a new inquiry.
THE POISONING OF NEW ZEALAND
http://www.investigatemagazine.com/poisoning_of_new_zealand%20OCT2000.htm

Photo: The controversial GMO banana, funded by the Bill & Melinda Gates Foundation and being grown in Australia, has arrived in the U.S. for human feeding trials. Volunteers will be paid $900 to participate in this feeding trial, which will analyze blood samples to measure the impact on vitamin A levels before and after eating. Wendy White, the researcher at Iowa State University who is carrying out the study, is reluctant to discuss it. In an e-mail to NPR, she wrote that disclosing details about the study "could preclude me from publishing our findings in a peer-reviewed scientific journal." This leads us to ask several questions. First, why the secrecy? Second, what is the duration of the study - will it be a meaningful long term study? Third, will the study meet the criteria for a chronic toxicity study or will it only measure vitamin A levels? Lastly and most importantly, Americans have been involuntarily participating in GMO feeding trials without our knowledge or consent for almost 20 years. WHERE'S OUR MONEY????

READ: http://www.npr.org/blogs/thesalt/2014/07/08/325796731/globe-trotting-gmo-bananas-arrive-for-their-first-test-in-iowa

#GMO #Banana #HumanFeedingTrials #USA #Uganda #Australia #BillAndMelindaGates #GatesFoundation #MelindaGatesFoundation #VitaminA #labelgmos #boycottgmos #bangmos #GMOFreeCanada #GMOFreeUSA

Trade Agreement to Force GMOs and Pesticides on US MAY BE DERAILED!!!

Doctors and scientists call on German Chancellor Merkel to halt US-EU trade deal

on .
TTIP threatens public health and the environment, say experts
A GROUP OF German physicians and scientists has called on Chancellor Angela Merkel to use her influence to halt the TTIP trade deal between the US and Europe in the interests of public health and the environment.
The TTIP is being negotiated behind closed doors, away from public scrutiny. It threatens to drag Europe down to the same level as the US on GMO and food safety regulation, in the name of harmonising standards and removing trade barriers. Corporations will be able to sue governments that reject their risky products.
The growing trend of physicians and scientists speaking out in defence of public health and the environment is welcome. Another example is the 297 scientists and experts who signed a statement to the effect that there is no consensus on GMO safety.

Open letter to German Chancellor Dr. Angela Merkel

* Appeal to halt negotiations on the Transatlantic Trade and Investment Partnership (TTIP)
Dear Chancellor Dr. Angela Merkel,
On February 13, 2013, the US-American president and representatives of the European Union announced their intent to negotiate a Transatlantic Trade and Investment Partnership (TTIP) between the U.S. and the EU (also known as the Trans-Atlantic Free Trade Agreement/TAFTA).
With TTIP it is planned not only to remove tariffs (which, incidentally, are not particularly high), but, above all, to eliminate non-tariff trade barriers by aligning the different U.S. and the EU standards. These TTIP regulatory efforts would irrevocably change the foundation of our society and its future development.
Politicians as well as business leaders on both sides of the Atlantic are vigorously pursuing the TTIP. Negotiations are taking place behind closed doors and obviously under extreme time pressure. The treaty should be completed as early as 2015. We citizens are left out. All of this contradicts our understanding of a democratic society.
The U.S. journalist, Lori Wallach, commented on the project in Le Monde Diplomatique on November 8, 2013 as follows: “This Transatlantic Trade and investment Agreement (TTIP) intends to – similar to its predecessor MAI [Multilateral Agreement on Investment] – secure and broaden the privileges of corporations and investors. The US and the EU seek to align their respective standards in non-trade sectors. These "harmonisation" attempts serve, as expected, the interests of corporations and investors. If standards are not fulfilled, indefinite trade sanctions or gigantic compensation payments can be imposed.” The English journalist George Monbiot wrote in the Guardian on November 4, 2013 that “this transatlantic trade deal is a full-frontal assault on democracy” and of a treaty “that would let rapacious companies subvert our laws, rights and national sovereignty.”
The above-mentioned newspaper articles as well as television broadcasts (including Report München, Monitor) report on the problems of such an investor-state dispute settlement (ISDS), illustrating these with concrete examples. In addition, the media also demonstrates other hazards of the TTIP such as: lowering of European consumer protection and health standards; threats to agricultural, organic farming; openings for agro-biotechnology; reduction of social standards as well as climate and environmental protection requirements; new waves of privatisation in areas of basic public services and further deregulation of the financial sector.
The European Commission has responded to the legitimate concerns and fears of citizens and their loss of confidence in public policy making with targeted communication strategies (Managing Transparency, Leaked European Commission PR strategy). Nevertheless, so far 714,809 citizens have taken part in online petitions in opposition to TTIP in Germany. On May 22, 2014, these signatures were presented to the top candidates for the European Parliament by the action alliance ttip-unfairhandelbar. Numerous organisations (NGOs) on both sides of the Atlantic have made similar anti-TTIP appeals to decision makers.
From experience with previous free trade agreements and liberalisation, as well as from what has been leaked to the public concerning the current TTIP negotiations, we have also come to a position of concern about the TTIP between the U.S. and the EU.
We object to the aim of regulatory harmonisation that threatens current European environmental and health standards as well as the planned investor-state dispute settlement. It is unacceptable that, in investor-state dispute settlements, foreign investors may sue nations and governments for high compensation payments if laws reduce their profit expectations. This influence on legislation would be incompatible with principles of the rule of law and it is immoral.
Dear Madame Chancellor, we are therefore appealing to you to take a different political course, and to use your considerable influence to halt the TTIP negotiations. Rather than the TTIP and its risks and dangers to the common good we need a different orientation of policy. We are standing at the crossroads in many areas of society.
As an alternative to TTIP, it is essential to launch important future-oriented projects for a sustainable and viable society. Due to our responsibility as physicians and scientists, and as fathers and mothers, we therefore request:
* the creation of a social framework for responsible environmental resource management and its political implementation
* a consistent policy of GMO-free agriculture
* increased support for organic farming and organic farming research; the current minimal funding of organic farming is ecologically harmful and irresponsible towards future generations
* further development and implementation of the precautionary principle and improvements of appropriate standards for the reduction of health hazards caused by unhealthy food and environmental pollution
* that in matters relating to risk assessment and standardisation of products and processes, important environmental and health committees are made up of scientists independent of industry; the promotion of industry-independent research in these areas
* privacy policy and digital humanism rather than a surveillance state
* sovereignty in cultural policy and its promotion
* measures promoting a just society: the reduction of poverty among children and the elderly as well as the – between childhood and old age poverty – continuously growing working poverty; prevention of tax evasion; regulation of the financial sector; public accountability and responsibility for key areas of public services – health, education, water, housing, mobility, etc
In our striving to achieve a sustainable and viable society, we appeal to you to halt the secret TTIP negotiations.
Dear Madame Chancellor, our Constitution calls on you to prevent harm to the German people: We appeal to you to do this for us, our children, and grandchildren.
Prof. Dr. Dr. Karl-Frank Kaltenborn (Initiator), Marburg
Prof. Dr. Monika Krüger, Leipzig
Dr. Martha Mertens, München
PD Dr. Johannes Maria Becker, Marburg
Website: http://kritik-freihandelsabkommen.de/

RoundUp Feeds Plant Fungus Monsanto/USDA Hide Glyphosates Dangers to Health

The discovery that glyphosate enhances fungal growth contradicts several previous studies, including a 2007 study performed by US Department of Agriculture researchers,[4] which did not find that glyphosate increased Aspergillus flavus growth. The authors noted that their findings are consistent with research on similar fungal strains, such as Fusarium,[5] which possesses high tolerance to applied doses of glyphosate, and Rust fungi and Blight fungi,[6] [7] which exhibit enhanced growth on glyphosate-amended media.

A new study reveals that Roundup herbicide enhances the growth of aflatoxin-producing fungi, lending an explanation for the alarming increase in fungal toxins recently discovered in U.S corn, and revealing another way in which GM farming is seriously undermining food quality.
A new study lead by Argentinean researchers and published in the Journal of Environmental Science and Health titled, "Influence of herbicide glyphosate on growth and aflatoxin B1 production by Aspergillus section Flavi strains isolated from soil on in vitro assay,"[1] adds to an increasing body of research indicating that glyphosate (aka Roundup), the primary herbicide used in GM agriculture, is seriously undermining the quality of our global food supply, and may help to explain recent observations that GM corn heavy markets, such as the U.S., have a significant aflatoxin problem.[2]
Researchers from the Department of Microbiology and Immunology, National University of Rio Cuarto, Cordoba, Argentina, set out to evaluate the effect of glyphosate (Roundup) on the growth of aflatoxin B1 production by strains of Aspergillus under different water availabilities on maize based medium. Aflatoxin B1, one of at least 14 different types, is a naturally occurring mycotoxin that is produced by Aspergillus flavus and Aspergillus parasiticus, two species of fungi that commonly effect cereal grains.  Known to be one of the most carcinogenic substances in existence, aflatoxin B1 is classified by the International Agency for Research on Cancer (IARC) as "Group 1, carinogenic to humans," with an oral, rat LD50 (the dose that acutely kills 50% of a test group) of 5mg/kg – compare that to a 6.4 mg/kg LD50 for potassium cyanide, which is used in lethal injection.
The authors of the study pointed out that that little previous research has been performed on the role of glyphosate on the growth rate of aflatoxin-producing fungal species.  The researchers also described the relevance this information has to the Argentinean corn market:
"Aspergillus section Flavi and Nigri Argentina is the world's second biggest exporter of maize (Zea mays L.), and was responsible roughly for 15 percent of the world's maize exports in the last three years. During the harvest season 2011/2012 the maize production is expected to be of 20 million tons.  These cereal grains are colonize by several fungi communities, including mycotoxigenic species."
Argentina's total acreage dedicated to GM corn, while small in comparison to the U.S. majority stake in the world market, is second only to the U.S. [See figure 1]
Argentina's corn production versus global

Also, Argentina's GM corn share in the total GM corn acreage of their country is on par with the U.S. [see figured 2 below], indicating that their environmental and toxicological situation in regard to the food quality fallout from GM farming is likely very similar.
Figure 2: GM maize share in the total maize acreage of a country/Source: GMO-Compass.org

Researchers Discover Roundup Enhances Growth of Aflatoxin-Producing Fungi

In brief, the researchers discovered that all six different concentrations of glyphosate tested decreased the lag phase of fungi growth proportionately to the increase in glyphosate concentrations.  In other words, the glyphosate enhanced the growth of the aflatoxin-producing Apergillus strains, and at concentrations lower than the range generally detected in Argentinean soils destined to crop production, specifically an agricultural area belonging to the province of Buenos Aires.[3]
In the author's words:
"This study has shown that the eight Aspergillus flavus and A. parasiticus strains evaluated are able to grow effectively and produce AFs [aflatoxins] in natural medium with high nutrient status over a range of glyphosate concentrations under different aW [water activity] conditions."
The figure below shows the influence of glyphosate on growth and aflatoxin B1 production:
Aflatoxin Glyphosate
Figure 3: Influence of glyphosate on aflatoxin
The discovery that glyphosate enhances fungal growth contradicts several previous studies, including a 2007 study performed by US Department of Agriculture researchers,[4] which did not find that glyphosate increased Aspergillus flavus growth. The authors noted that their findings are consistent with research on similar fungal strains, such as Fusarium,[5] which possesses high tolerance to applied doses of glyphosate, and Rust fungi and Blight fungi,[6] [7] which exhibit enhanced growth on glyphosate-amended media.

Abstract:
The effect of six glyphosate concentrations on growth rate and aflatoxin B1 (AFB1) production by Aspergillus section Flavi strains under different water activity (aW) on maize-based medium was investigated. In general, the lag phase decreased as glyphosate concentration increased and all the strains showed the same behavior at the different conditions tested. The glyphosate increased significantly the growth of all Aspergillus section Flavi strains in different percentages with respect to control depending on pesticide concentration. At 5.0 and 10 mM this fact was more evident; however significant differences between both concentrations were not observed in most strains. Aflatoxin B1 production did not show noticeable differences among different pesticide concentrations assayed at all aW in both strains. This study has shown that these Aspergillus flavus and A. parasiticus strains are able to grow effectively and produce aflatoxins in high nutrient status media over a range of glyphosate concentrations under different water activity conditions.

Thursday, July 10, 2014

RNAi Ebola FDA Clinical Hold

...a leading developer of RNA interference (RNAi) therapeutics, today announced that the Company has received verbal notice from the U. S. Food and Drug Administration (FDA) that the TKM-Ebola Phase I healthy volunteer clinical study has been placed on clinical hold. This notice applies only to this study.

Joint Project Manager Medical Countermeasure Systems (JPM-MCS) U.S. Department of Defense (DoD)
In 2010, Tekmira signed a $140-million contract with the DoD to advance an RNAi therapeutic, which utilized our LNP technology, to treat Ebola virus infection. In 2013, the collaboration was expanded to include significant advances in LNP formulation technology, including a new LNP formulation that was more potent, the ability to be able to lyophilize (freeze-dry) LNP formulations and an LNP formulation that can be administered subcutaneously. In January 2014, Tekmira commenced TKM-Ebola Phase I clinical trial. JPM-MCS, a component of the Joint Program Executive Office for Chemical and Biological Defense, aims to provide U.S. military forces and the nation with safe, effective, and innovative medical solutions to counter chemical, biological, radiological, and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance U.S. biodefense response capability. For more information, visit www.jpeocbd.osd.mil. Read more about TKM-Ebola here.

Monsanto Company

In 2014, Tekmira signed an Option Agreement with Monsanto, permitting Monsanto to obtain a license to use Tekmira's proprietary delivery technology. The companies' agreement and research collaboration will focus on the development of new innovative biological solutions for farmers, which have the potential to provide new options for sustainable pest, virus and weed control. The potential value of the transaction could reach up to $86.2 million following the successful completion of milestones.

Monsanto (MON) pays Tekmira Pharmaceuticals (TKMR) $1.5M for a milestone related to the research program under the Option Agreement the two companies signed in January covering Tekmira's proprietary delivery technology and IP for use in agricultural applications. The potential value of the agreement could be as high as $86.2M if all program milestones are met.

Bristol-Myers Squibb

In 2010, Tekmira entered into a multi-year, target validation agreement with Bristol-Myers Squibb. Tekmira will supply LNP formulations of siRNA provided by Bristol-Myers Squibb to silence target genes of interest. Bristol-Myers paid Tekmira $3-million concurrent with the signing of the agreement. Tekmira announced a further expansion of the collaboration to include broader applications of its LNP technology and additional target validation work.


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY)

Tekmira has granted a license to Alnylam to use Tekmira's LNP technology to enable RNAi therapeutic products. Tekmira will receive milestone and royalty payments as these LNP-enabled products are developed and commercialized. Alnylam currently has three LNP-enabled products in human clinical trials: ALN-TTR02, ALN-VSP, and ALN-PCS02. Read more about Tekmira’s Partnered Products here.


About Small interfering RNA

Small interfering RNA (siRNA) are synthetic RNA molecules designed to suppress the production of proteins through RNA interference (RNAi). Sequencing of the human genome has provided the information needed to design siRNA therapeutics to target a wide range of disease-causing proteins. In fact, a siRNA therapeutic can be designed in a shorter time frame than synthesizing and screening conventional small molecule drugs. Further, siRNA-based therapeutics can bind to a target protein mRNA with great specificity. When siRNA are introduced into the cell cytoplasm, they are rapidly incorporated into an RNA-induced silencing complex (RISC) and guided to the target mRNA. The RISC cuts and destroys the target mRNA, preventing the subsequent production of this specific protein. The RISC can remain stable inside the cell for weeks, destroying many more copies of the target mRNA and suppressing this specific protein for long periods of time.

Tekmira has a worldwide license for the discovery, development and commercialization of RNAi products using siRNA directed to 13 gene targets.

Implications of Ebola data for Tekmira HBV Program

Like it or not, it is the HBV program that is driving the interest in Tekmira, at least in the near-term.  Therefore, the 15% sell-off in the stock yesterday following the Clinical Hold imposed by the FDA can be interpreted to be due to the uncertainty of what it means for the HBV program.

It is my working hypothesis that for the treatment of HBV via the immune reactivation pathway, the use of even transient immune suppression is to be avoided.  On the other hand, the recent Ebola clinical results by Tekmira suggest that transient immune suppression may also be desirable for 3rd gen SNALP delivery.  As TKM-HBV is expected to utilize '3rd gen' SNALP delivery, too, the Ebola results with immune activation seem like a bad omen.

While this cannot be ignored, there are a few reasons to believe that this might be too simplistic.

1.       Difference in dose

Although there was an apparent tendency for immune stimulation throughout the dose escalation with TKM-EBOLA, it was only at the high dose of 0.5mg/kg where a dose-limiting toxicity was observed. And according the yesterday's press release on the Clinical Hold, it is in particular cytokine elevations that were observed at 'higher doses' that are the issue.  

 Since unlike Ebola, HBV only replicates in hepatocytes, and because SNALP potency is highest in hepatocytes, the efficacious dose for HBV may be well below 0.5mg/kg with 3rd gen formulations.  Of note, even 2nd gen SNALPs are highly effective at 0.3mg/kg based on the Tekmira-enabled ALN-TTR02 candidate now in phase III.

2.       Different sequence, different immune stimulation

It is known (e.g. Judge et al. 2005Sequence-dependent immune stimulation of the mammalian innate immune response by synthetic siRNAs) that immune stimulation by RNAi, especially when liposomally formulated, is highly dependent on the actual sequence and modification pattern of the RNAi trigger.  Since TKM-EBOLA and TKM-HBV are different in that regard, it is well possible that while one 3rd gen formulation is immunostimulatory, the other is not.

3.       Immunostimulatory by design/by screen

Scientifically, I was most disappointed by the Ebola immune stimulations as Tekmira made a big deal in the wake of similar observation in 2010 with TKM-ApoB that with improved, more predictive immune stimulation assays, they would now be able to screen out the immunostimulatory formulations.  In a black-and-white world you would conclude ‘obviously not!’.

In a world of shades of grey, I can imagine that TKM-EBOLA might have happened to slip through this part of the screening process.  The reason is that since Ebola infects a number of cell types besides hepatocytes (endothelial cells, phagocytes etc), the impressive efficacy of TKM-EBOLA always stood out as something quite unusual.  So while containing the spread of the virus by hitting it particularly hard in the liver might be part of the mechanism, I am quite receptive to the notion that the scientists did not mind all that much some immune stimulation when the RNAi formulation had so much efficacy.
With HBV, however, the company might be much more careful in screening out immunostimulatory potential.

I can now hear Sarepta investors yell ‘it’s an artefact’, but I would caution them that Sarepta and the morpholino field at large is proposing morpholinos with cationic appendices for infectious diseases while these are not really considered for genetic diseases.  What I don’t understand is that why a modification that is supposed to be helpful in e.g. suppressing viral gene expression should not likewise be useful for suppressing human gene expression.  So maybe the value of these modifications is in tickling the immune system?

Seralini Study Restored to Academia

...restores the study to the peer-reviewed literature so that it can be consulted and built upon by other scientists.

The study found severe liver and kidney damage and hormonal disturbances in rats fed the GM maize and low levels of Roundup that are below those permitted in drinking water in the EU. Toxic effects were found from the GM maize tested alone, as well as from Roundup tested alone and together with the maize. Additional unexpected findings were higher rates of large tumours and mortality in most treatment groups.

The study was first published in Food and Chemical Toxicology (FCT) in September 2012[1] but was retracted by the editor-in-chief in November 2013 after a sustained campaign of criticism and defamation by pro-GMO scientists.[2]

Now the study has been republished by Environmental Sciences Europe. The republished version contains extra material addressing criticisms of the original publication. The raw data underlying the study’s findings are also published – unlike the raw data for the industry studies that underlie regulatory approvals of Roundup, which are kept secret. However, the new paper presents the same results as before and the conclusions are unchanged.


Comments from scientists


Dr Michael Antoniou, a molecular geneticist based in London, commented, “Few studies would survive such intensive scrutiny by fellow scientists. The republication of the study after three expert reviews is a testament to its rigour, as well as to the integrity of the researchers.

“If anyone still doubts the quality of this study, they should simply read the republished paper. The science speaks for itself.

“If even then they refuse to accept the results, they should launch their own research study on these two toxic products that have now been in the human food and animal feed chain for many years.”

The Glyphosate Aluminum Cage

Glyphosate cages all kinds of things. One of the things it does in the gut is it cages all the minerals, like iron and manganese and even sulfur, so it prevents the gut bacteria from gaining access to really important micronutrients.  Even things like molybdenum which we only need in small amounts, and we need these minerals for certain enzymes.  Glyphosate builds a cage around them and it builds a cage around aluminum as well.
Autism
...The aluminum ends up accumulating, getting trapped with the glyphosate, and then the aluminum ends up in the pineal gland, and messes up sleep, and causes a whole cascade of problems in the brain. The glyphosate and aluminum are working together to be much more toxic than they would be, acting alone.
Kidney failure
...sugarcane fields in Sri Lanka and in El Salvador are sprayed with glyphosate right before the harvest just as wheat is and the workers are dying at a young age from kidney failure. People with Celiac disease are at a high risk of kidney failure and Seneff can see how glyphosate would kill the kidney, because you get into an overgrowth of pathogenic bacteria that produces p-cresol, which is very toxic to the kidney.
Celiac Gluten Sensitivity
...glyphosate binds to the gluten. Gluten usually forms cross-mesh connections between different amino acids, and glyphosate would disrupt that because it would prevent the cross-mesh by binding to the gluten and causing the gluten to stay in the form that is known to be more allergenic. So she believes that glyphosate causes the gluten to assume the form that is more allergenic and this applies to both Celiac disease and gluten sensitivity.
MIT senior research scientist, Stephanie Seneff

Safer Than Ever EU/Monsanto Glyphosate Re-assessment

 "Monsanto and a consortium of European chemical companies that performed the risk assessment for the re-approval of glyphosate....
...glyphosate poses no unacceptable risks. Glyphosate is not metabolized or accumulated in the body, not genotoxic, not carcinogenic, not endocrine disrupting, and not considered persistent or bioaccumulative; it has no reproductive toxicity, no toxic effects on hormone-producing or hormone-dependent organs, and no unacceptable effect on bees. Therefore any risks are within acceptable standards.  The only risks noted were that glyphosate is a severe eye irritant and is persistent in soil.
Issues that could not be finalized in the assessment were: relevance of impurities, effects on microorganisms, effects on non-targeted plants, and indirect effects on biodiversity - non-targeted organisms, particularly birds.
The Proposed Decision at the end of Vol. 1 is completely blacked out.
...How did they arrive at such a preposterous conclusion when the evidence for glyphosate herbicides toxicity has accumulated worldwide to such an extent that a number of countries are already banning its use?
...Denmark took the lead to ban the herbicide back in 2003 [2] The Dutch Parliament banned it in April 2014 for non-commercial use [3], to take effect by the end of 2015; France is set to follow. Brazil, one of the largest growers of glyphosate-tolerant genetically modified (GM) crops has now filed a law suit by Federal Prosecutors to ban glyphosate along with 8 other dangerous pesticides [4]. El Salvador imposed a complete ban in February 2013, linking glyphosate herbicides to an epidemic of chronic kidney disease that has struck the region [5]. Sri Lanka’s scientists have provided evidence for glyphosate accumulation in the body especially in the presence of hard water. Its ability to capture and retain arsenic and nephrotoxic metals enables it to act as a carrier to deliver the toxins to the kidney [6] (see [7] Sri Lanka Partially Bans Glyphosate for Deadly Kidney Disease Epidemic, SiS 62). The Sri Lankan government initially instituted a ban, but reneged under pressure from industry [8]. 
Glyphosate has also been linked to many other health problems including cancers (see [9] Glyphosate and CancerSiS 62), infertility (see [10] Glyphosate/Roundup & Human Male InfertilitySiS 62), along with neurotoxicity, reproductive problems, birth defects, genotoxicity, and other human health problems as well as ecotoxicity (see [11] Ban GMOs Now, special ISIS report), and many have considered a world-wide ban long overdue.

Glyphosate Task Force (GTF) [19].   And the GTF consists of Monsanto and a consortium of chemical companies all over Europe, including Syngenta UK and Dow Italy, with an odd one from Taiwan thrown in for good measure (see pp. 9-13 of Vol. 1 of the RAR [13]). Although the BfR added comments here and there, all the assessments of the toxicological studies were from the GTF. Hence Monsanto and other companies who stood to gain from selling glyphosate herbicides were given free rein to pronounce glyphosate effectively even safer than before, hence the increase in ADI.
Let us be clear: even the industry’s studies found toxic effects for acute (single dose), subchronic (short-term) and chronic (long-term) exposures at some dosage. The way the game is played is to vary the dose and find the maximum dose where no adverse effects are observed (NOAL). Then divide that by 100 to obtain the ADI and declare the substance “safe”. The chemical industries already knowthat glyphosate is toxic and can cause a host of physical problems.

...The entire process of risk assessment for re-approval was flawed and corrupt to the core. It is rife with conflict of interest, non-transparent and heavily biased towards unpublished, non-peer reviewed studies from industry. The RAR is worse than useless, and should be rejected outright.  All available evidence including studies on commercial formulations of glyphosate herbicides should be seriously considered in any risk assessment, and by a truly independent, unbiased panel free from any conflict of interest."

Science, Society, Sustainability

Wednesday, July 9, 2014

EPA is Sued Cyantraniliprole Approval Farce

"Despite specific comments urging EPA to consult and EPA's conclusions in the Risk Assessment that additional analyses and cooperation with the Services were necessary, EPA finalized its CTP Registration Decision without consulting with NMFS or FWS as required by Section 7 of the ESA [Endangered Species Act]," states the complaint.
The groups say the government's authorization of the pesticide violates the Endangered Species Act. They want a court order vacating the EPA authorization of CTP use.
The groups' lead counsel is Patti Goldman, with Earthjustice, of Seattle.
http://www.cnsenvironmentallaw.com/2014/06/05/2500.htm

The EPA registered the pesticide in January, including product mixtures containing other pesticides such as thiamethoxam.
Photo: Summer Solstice comes at the precise moment when the sun’s power is at its peak. Solstice means ‘sun stands still’ because the sun rises and sets in the same spot for a few days. Here in the northern hemisphere, this is the longest day and shortest night of the year. From then on, the days will get shorter. This phenomenon is a direct result of the Earth-Sun relationship. After peaking, the Sun begins to wane, and the journey into the harvest season begins. 

It has always been an important solar event throughout the evolution of humankind. The axis of Stonehenge and the Temple of the Sun in Mexico are both oriented in the direction of the Midsummer sunrise.

Astrologically the Summer Solstice corresponds to the entry of the Sun into Cancer, interestingly a water sign governed by the moon. Cancer symbolizes the moving waters of our inner life, our moods and cycles, our instincts, intuition, 
our juiciness. It is the force & power of our imagination, our emotions, our roots. A reflective, passive, cyclic force, this sign marks the intimate inner world, personal & family bonds, as well as our larger collective family, with an accent on the tribe, the clan, and a sense of belonging. 

The Festival of Summer Solstice is sometimes called Midsummer’s Eve or St. John’s, and it is celebrated like other ‘holy days’ on the Eve, starting at twilight, when the power is most concentrated. 

Midsummer’s Eve is a magical time to communicate with the plant & fairy spirits, as it is the time of the herb harvest. All plants gathered this night are considered exceptionally potent for healing and ritual purposes.

St. John’s Wort & other healing herbs are placed around the home for protection as they dry. They are also thrown into the Midsummer bonfire, and when the coals have cooled down the ashes are mixed with water and sprinkled on the fields, the 4 corners of the home, and the on the head or feet of the children. 

Royal fern seeds gathered at midnight on the eve are said to make you invisible; rub the blossoms on your eyelids to see the wee folk, which will also make you wealthy and wise, but be sure to carry a bit of rue in your pocket or you might be ‘pixie-led’. Can’t find the rue, then turn your jacket inside out and follow the old ‘Ley-Lines’, which will keep you from getting lost in fairy land. 
Divination on matters of love are especially powerful on Midsummer’s Eve. Young women place yarrow or other herbs and flowers native to their part of the world peaking at this time, under their pillows, to dream of their future mates. 

Called St. John’s Eve by the church, this is traditionally the time when the herb St. John’ Wort reaches its full potency. Since it is a solar herb, it is used to bring the power of the sun to people who suffer from depression.      

The ancient Druids celebrated the Summer Solstice as the Wedding of Heaven and Earth. The Goddess manifests as Mother Earth & the God as the Sun King.

In even earlier times, the sun was perceived in its shinning prime and glory –
giver of light and heat and life, as the effulgent force of the Feminine - 
a passionate aspect of the versatile Great Mother, who issues forth & supports all life. 

The Solar Goddess was known in many ancient cultures and Her Priestess’ were highly regarded as healers and Psychopomps - Spiritual guides, initiating supplicants into the mysteries hidden behind the blinding light and fire of the solar disk. They used the 1st mirrors or lenses to harness the sun, to start the altar fires and to cauterize wounds for healing.

During the time of the ancient Egyptians, Sirius, the Dog Star rose on the Summer Solstice, heralding the beginning of their new year, just before the season of the Nile’s flooding.

The sun itself was deemed to be the all-seeing, all knowing, all powerful eye; but It was also known to be the “scorching eye of Ra” burning away the shadows, like a laser in the hands of a surgeon, cutting away disease, a power not to be taken (pardon the pun) lightly. 

Probably the most ancient source of the Solar Force known to humanity is an Egyptian lion-headed Goddess called Sekhmet. She displays all the passion of the noonday-sun at its peak, burning away all that does not serve, rousing us to dance our true power, in the magic ritual of our transformation.

Solar energy & its radiations are said to be the cause of evolution itself, reminding us that we can take an active role in our evolutionary process by aligning ourselves with this Solar Power, plugging in directly to the source of ourselves, to the source of action and passion.

But remember, at this time of the zenith, the brightest light, casts the deepest shadow. 

~Hazel Archer Ginsberg, Festivals Coordinator & Council Member of the Chicago Rudolf Steiner Branch




Cyantraniliprole; Pesticide Tolerances
This is how it works...I took the time to find out...Even read the entire paper!
ACTION...Final Rule.
SUMMARY...This regulation establishes tolerances for residues of cyantraniliprole in or on multiple commodities that are identified and discussed later in this document. E.I. du Pont de Nemours & Company (DuPont) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

ϟ ...a quantitative acute dietary exposure assessment is unnecessary.

ϟ ...dietary exposure assessment for the purpose of assessing cancer risk is unnecessary

ϟ ...data be provided 5 years after the tolerance is established,

ϟ ...An acute dietary risk assessment was not conducted

ϟ ...intermediate-term exposures are not likely because of the intermittent nature of applications by homeowners.

ϟ ...In addition, the submitted data support the conclusion that the effects on the thyroid are secondary to effects on the liver.

ϟ ...Post-application incidental oral exposures for children may occur for short- and intermediate-term durations due to the persistence of cyantraniliprole. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at EPA.

ϟ ...EPA has assumed that cyantraniliprole does not have a common mechanism of toxicity with other substances.

ϟ ...no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.

ϟ ...No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, cyantraniliprole is not expected to pose an acute risk.

ϟ ...2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to cyantraniliprole from food and water will utilize 50% of the cPAD for children 1-2 years old (the population group receiving the greatest exposure) and 22% of the general U.S. population.

ϟ ...Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to cyantraniliprole residues.

ϟ ...In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for departing from the Codex level. Currently there are no Codex MRLs for cyantraniliprole.

ϟ ...Therefore, tolerances are established for residues of cyantraniliprole, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1 H-pyrazole-5-carboxamide, including its metabolites and degradates, in or on....