30 Scientists Accuse Tufts Researchers of Ethical Violations-- Nuremberg Code

30 Scientists Accuse Tufts Researchers of Ethical Violations-- Nuremberg Code



ALLIANCE FOR HUMAN RESEARCH PROTECTION
A Catalyst for Public Debate: Promoting Openness, Full Disclosure, and Accountability
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FYI
A report in the business forum, Zikkir, "Out of Sight" was prompted by the publicity surrounding the $79 million settlement of Pfizer's unethical Trovan experiment conducted on Nigerian infants.
http://www.ahrp.org/cms/content/view/571/72/.



The Zikkir article touches on the problems related to the US pharmaceutical industry's increased outsourcing of clinical trials to off-shore locations, mostly in underdeveloped countries including Eastern Europe and Russia which do not conform to ethical restraints mandated by the Nuremberg Code or the Declaration of Helsinki. http://zikkir.com/business/6259?wscr=1024x768.



An in-depth report by the Institute of Science in Society, "The Golden Rice
Scandal Unfolds," demonstrates that academics who are shielded by the US
government seal of approval, have been conducting medical experiments that
are clearly prohibited by the Nuremberg Code. The article focuses on a
series of recent unethical Phase II trials conducted by Tufts University
researchers, who tested genetically modified "Golden Rice' (GR2) on children
in the U.S. exposing them to "an unapproved experimental genetically
modified rice enhanced in pro-Vitamin A that has the potential to cause
birth defects and developmental abnormalities."

The questionable experiments-which ISIS described as "an exercise in how not to do science"--are:

1. Project NCT 00680355.(10) Bioavailability of Golden Rice Carotenoids in Humans.
http://clinicaltrials.gov/ct2/show/record/NCT00680355?term=golden



2. Project NCT 00082420. Retinol Equivalence of Plant Carotenoids in Children.
http://clinicaltrials.gov/archive/NCT00082420

The experiment compared the vitamin A value of b-carotene in oil capsule, spinach and Golden Rice - recruited 72 children 7 to 9 years of age. The starting date of the experiment was September 2004, it ended November 2005.

3. Project NCT 00680212. Vitamin A Equivalence of Plant Carotenoids in Children.
http://clinicaltrials.gov/ct2/show/record/NCT00680212?term=golden


In this experiment, researchers recruited 72 children 6 to 8 years of age and registered start and finish dates July 2008 and January 2009.

The ISIS report (submitted to the FDA in March, 2009) states:
"The Golden Rice Project website [6] (accessed 17 March 2009), stated that "Golden Rice has gone through many tests since it was first obtained" Nine items are listed; but no feeding trial on animals among them." See: http://www.i-sis.org.uk/goldenRiceScandal.php



"Golden Rice" has been touted as a humanitarian effort to resolve vitamin A deficiency. However, it has met with significant opposition from environmental and anti-globalization activists who view it as a commercial threat.

For example, Dr. Vandana Shiva called it "a hoax:"

"Unfortunately, Vitamin A rice is a hoax, and will bring further dispute to plant genetic engineering where public relations exercises seem to have replaced science in promotion of untested, unproven and unnecessary technology."

"The problem is that vitamin A rice will not remove vitamin A deficiency (VAD). It will seriously aggravate it. It is a technology that fails in its promise.

Since the daily average requirement of vitamin A is 750 micrograms of vitamin A and 1 serving contains 30g of rice according to dry weight basis, vitamin A rice would only provide 9.9 micrograms which is 1.32% of the required allowance. Even taking the 100g figure of daily consumption of rice used in the technology transfer paper would only provide 4.4% of the RDA."

"In order to meet the full needs of 750 micrograms of vitamin A from rice, an adult would have to consume 2 kg 272g of rice per day. This implies that one family member would consume the entire family ration of 10 kg. from the PDS in 4 days to meet vitaminA needs through "Golden rice".

"This is a recipe for creating hunger and malnutrition, not solving it."

"Even the World Bank has admitted that rediscovering and use of local plants and conservation of vitamin A rich green leafy vegetables and fruits have dramatically reduced VAD threatened children over the past 20 years in very cheap and efficient ways."
See: THE "GOLDEN RICE" HOAX -When Public Relations replaces Science
http://online.sfsu.edu/~rone/GEessays/goldenricehoax.html



The ISIS report calls the Tufts experiments "morally inexcusable:"

"The phase II clinical trials of uncharacterized, unapproved, experimental GR2 events on children, some of whom may indeed be suffering from vitamin A deficiency, is morally inexcusable. GR2 has not been assessed for safety, and there are reasons to suspect it is unsafe."
See: http://www.i-sis.org.uk/goldenRiceScandal.php



In February, 2009, an open letter addressed to Professor Robert Russell, Professor Emeritus, Friedman School of Nutrition Science and Policy, Tufts University School of Medicine (Email: rob.russell@tufts.edu) was signed by 30 senior scientists who protested the unethical testing of a possibly hazardous substance--"Golden Rice" (GR2) in children.

The letter states that the trials

"appear to be an experimental collection of transgenic events still in the laboratory, uncharacterized in terms of basic molecular genetics or biological and biochemical properties, not tested pre-clinically on animals, or subjected to any other safety assessment."

"The variety of Golden Rice used in these experiments (GR2) is inadequately described in terms of biological and biochemical characterization. anywhere else in the publicly available literature, and has woefully inadequate pre-clinical evaluation."

" It is a genetically modified product which has not been shown to be distinctive, uniform and stable over time. It has never been through a regulatory /approvals process anywhere in the world. There is now a large body of evidence that shows that GM crop/food production is highly prone to inadvertent and unpredictable pleiotropic effects, which can result in health damaging effects when GM food products are fed to animals (for reviews see Pusztai and Bardocz , 2006; Schubert, 2008; Dona and
Arvanitoyannis, 2009)."

"More specifically, our greatest concern is that this rice, which is engineered to overproduce beta carotene, has never been tested in animals, and there is an extensive medical literature showing that retinoids that can be derived from beta carotene are both toxic and cause birth defects."

No results have been made available for either of the pediatric studies (as of 17 March 2009).

The scientists noted that the three Tufts Projects breached the Nuremberg Code / medical ethics code "on a number of counts, and we urge you to call them to a halt immediately."

"They should not be resumed unless and until the researchers can demonstrate that a full range of laboratory and animal feeding trials have been completed and published for the Golden Rice strain being used, and unless and until appropriate regulatory bodies have had an opportunity to come to a view on the health and safety issues about which we are very concerned."

"We can assure you that such trials would not have been approved within the European Union in the absence of safety information, which highlights yet again the flaw of the USDA and FDA regulatory system in considering GM crops/foods as hypothetically "generally recognised as safe - GRAS" in the
absence of hard experimental data."

Further underscoring the U.S. academics' and government agency disregard for medical ethics, the ISIS report notes that an Indian newspaper reported that a clinical trial was cut short in China in July 2008, when the government found that 24 children 6-8 years of age at a primary school in Henyan, Hunan, were to be used as guinea pigs for a trial with Golden Rice."

That trial was also sponsored by Tufts University and approved by the US National Institute of Health--though not from the Chinese government, which was alerted by Greenpeace. Greenpeace has also warned the governments of Bangladesh, India, Indonesia, Philippines and Vietnam against the risky trials.

It would appear that the Chinese government conforms to higher medical ethics standards than the US National Institute of Health.

So, why has the media failed to pay any attention to these morally deplorable human experiments on American children ?

Contact: Vera Hassner Sharav
veracare@ahrp.org
212-595-8974

http://www.i-sis.org.uk/goldenRiceScandal.php


ISIS Report 18/03/09

The Golden Rice Scandal Unfolds

Phase II clinical trials on children have been conducted with unapproved experimental GM rice enhanced in pro-Vitamin A that has the potential to cause birth defects and developmental abnormalities Dr. Mae-Wan Ho and Prof. Joe Cummins

This report has been sent to the United States Food and Drug Administration on behalf of ISIS

Clinical trials of unapproved, uncharacterized GM rice on children

EXCERPT:
According to a recent report [9], a sample of the Golden Rice grains was sent to Germany in 2001 for a feeding trial with mice. But when the grains were tested for carotenoid content, the scientists were "surprised to find it contained less than one percent of the amount expected." After the rice was cooked, this was reduced by another 50 percent, so the trial was abandoned.

In 2005, Syngenta made GR2 [10] using the maize version of the enzyme phytoene synthase that was transferred from daffodil. GR2 produced up to 23 times the amount of carotenoids in the original Golden Rice, GR1.

But GR2 was not a transgenic variety based on a single transformation event.  On the contrary, it was explicitly stated that [10]: "The reported transgenic rice events [emphasis added] are experimental." There is no telling whether all the children or adults taking part in any of the trials
were given Golden Rice from the same GR2 event.  The results of the trials, as yet unreleased, could well be utterly worthless.

Syngenta was donating these GR2 events, via the Humanitarian Project for Golden Rice, for further research and development (to institutes across China, India, Philippines, Indonesia, Bangladesh and Vietnam) "through license under certain conditions", which include "being governed by the
strategic direction of the Golden Rice Humanitarian Board" Requests were to be directed to Adrian Dubock, a previous employee of Syngenta.

Dubock helped Potrykus and Beyer work out a deal in which Syngenta could develop Golden Rice commercially, but farmers in developing countries who make less than US$10 000 a year could get it for free [5]. Dubock retired from Syngenta in 2007, but remains a member of the Golden Rice Humanitarian Board, chaired by Potykus.

Golden Rice, an exercise in how not to do science

Golden Rice, genetically modified to make pro-vitamin A in the endosperm (the grain remaining after polishing), was announced with great fanfare in 2000 as a cure for widespread vitamin A deficiency in developing countries.

The project had already cost US$100 million, funded by the Rockefeller Foundation, the Swiss Federal Institute of Technology, the European Community Biotech Programme and the Swiss Federal Office for Education and Science, and could cost as much again to develop. It was tied up in at least 70 patent claims on genes, DNA sequences and constructs, a problem only partly solved in the "ground-breaking deal" worked out by Dubock (see above)..

Condemnation was swift and widespread, not least because it was absurd to offer Golden Rice as the cure for vitamin A deficiency when there are plenty of alternative, infinitely cheaper sources of vitamin A or pro-Vitamin A, such as green vegetables and unpolished coloured rice (especially black and purple varieties [11], which would be rich in other essential vitamins and minerals, and hence much more nutritious. The UN Food and Agricultural Organization (FAO) started a project in 1985 to deal with vitamin A deficiency using a combination of food fortification, food supplements and general improvements in diets by encouraging people to grow and eat a variety of green leafy vegetables. One main discovery from the project was that the absorption of pro-vitamin A depends on the overall nutritional status, which in turn depends on the diversity of the food consumed [12].

The main cause of hunger and malnutrition in the Third World is the industrial monocultures of the Green Revolution, which obliterated agricultural biodiversity and soil fertility, resulting in ever-worsening mineral and micronutrient deficiencies in our food. Golden Rice, like other GM crops, is industrial monoculture only worse, and will exacerbate this trend, as well as the destruction of agricultural land, and the impoverishment of family farmers that also accompanied the Green Revolution [13] (see Beware the New "Doubly Green Revolution", SiS 37).

GR1 was made with the standard 'first generation' genetic modification techniques, using GM constructs that cause uncontrollable mutations and other collateral damage to the host plant genome, with many unintended, uncharacterized effects [14]. In addition, the viral and bacterial sequences, including antibiotic resistance marker genes, in the construct and in the vectors created for gene transfer enhance horizontal gene transfer and recombination, the main route to creating new pathogens and spreading antibiotic resistance.

GR2 represents an improvement in so far as antibiotic resistance markers were no longer used, but still includes a medley combination of sequences\ from plant pathogens Agrobacterium (used in a binary vector system) and Erwinia uredovor, and from E. coli, inhabitant of the human gut, which also contains pathogenic strains. We have highlighted the special hazards of the Agrobacterium vector system since 2003 [15] (Agrobacterium & Morgellons Disease, A GM Connection?, SiS 38) (see below).  The main reason for Golden Rice was revealed in the unusually long news feature article [16] accompanying the scientific publication [8] which stated: "One can only hope that this application of plant genetic engineering to ameliorate human misery without regard to short-term profit will restore this technology to political acceptability."

A detailed audit on the project [14] (The 'Golden Rice', An Exercise in How Not to Do Science, ISIS Report) uncovered "fundamental deficiencies" from the scientific and social rationale to the science and technology involved.  It was being promoted "to salvage a morally as well as financially bankrupt agricultural biotech industry." The situation has changed little since.

The phase II clinical trials of uncharacterized, unapproved, experimental GR2 events on children, some of whom may indeed be suffering from vitamin A deficiency, is morally inexcusable. GR2 has not been assessed for safety, and there are reasons to suspect it is unsafe.  GMO safety in question

The biotech industry has consistently found genetically modified food and feed 'as safe as their conventional counterparts', and regulators in the United States and European Union have accepted this assertion overwhelmingly based on studies carried out and interpreted by the industry [17] (GM Food Nightmare Unfolding in the Regulatory Sham, ISIS scientific publication).

There is now a string of evidence that exposure of many species of animals to a variety of genetically modified crops, and food and feed derived from them, can cause illnesses and death, raising the distinct possibility that genetic modification is inherently dangerous [18] (GM is Dangerous and Futile, SiS 40). This is reinforced in results obtained in the most recent studies.
....
Golden Rice particularly dangerous

In addition, the unbalanced enhancement of single nutrients in GM crops may do more harm than good [27] (GM Crops and Microbes for Health or Public Health Hazards? SiS 32). As David Schubert at the Salk Institute for Biological Sciences La Jolla, California, in the United States points out [28], plants possess the ability to synthesize between 90,000 and 200,000 nonessential small molecules, with up to 500 in one species. The enormous repertoire is due in part to enzymes with very low substrate specificity, which are unpredictably altered by mutations and pleiotropic effects associated with GM technology. Furthermore, overdose of many single nutrients are known to be toxic, vitamin A being a case in point. Schubert highlights the toxic effects of retinoic acid and other metabolites of b-carotene, only a few of them can be identified and measured in the current state of technology.

Golden Rice is enhanced in b-carotene, which on ingestion, is cleaved in half to generate retinal for use in the visual cycle. Retinal is also reduced to retinol, or oxidized to retinoic acid (RA), which interacts with highly specific nuclear receptors. Essentially all of the biological activity of retinoids, apart from vision, involves RA. While high concentrations of retinol are toxic, RA is biologically active at concentrations several orders of magnitude lower than retinol. Hence, Schubert states [28]: "excess RA or RA derivatives are exceedingly dangerous, particularly to infants and during pregnancy." RA is required for the development of the nervous system, both by directly controlling nerve differentiation and by generating concentration gradients that direct cell migration, embryonic segmentation, and development. Therefore, RA and synthetic derivative of RA are teratogenic (able to cause birth defects).  They can accumulate in fat and plasma, becoming a risk factor for pregnancy for up to 2 years following ingestion, and multiple low doses of retinoids have greater toxicity than a single high dose.

Because of the type of biological functions controlled by low levels of RA, any perturbation of its signalling pathways by plant-derived RA receptor agonists or antagonists will have clinical consequences. "Could the GM modifications used to enhance b-carotene synthesis create such compounds?"
(This question remains unanswered to this day.) Six hundred naturally occurring compounds exist in the carotene family, and at least 60 can be precursors to retinoids. "Therefore, plants have the potential to make many potentially harmful retinoid-like compounds when there are increased levels of synthetic intermediates to b-carotene as in golden rice."

While all retinoids and derivatives are likely to be teratogenic, good assays and information regarding the behaviour and teralogic activity are available for only three: retinol, RA, and retinal. Therefore, at the very least, "extensive safety testing should be required before the introduction of golden rice as a food."

See complete ISIS report with copious references at:
http://www.i-sis.org.uk/goldenRiceScandal.php



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