The Golden Rice Scandal Unfolds

Dr. Mae-Wan Ho and Prof. Joe Cummins

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

EXCERPT:

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.

The Austrian government commissioned long term studies showing that mice fed GM maize hybrid (NK603xMON810) with combined glyphosate tolerance and biopesticide Cry1Ab produced fewer and smaller litters with many genes affected compared to controls [19] (GM Maize Reduces Fertility & Deregulates Genes in Mice, SiS 41). At the same time, the Italian National Institute of Research published a study showing that GM maize MON810 fed to mice produced disturbances in the immune system of the young and the old [20] (GM Maize Disturbs Immune System of Young and Old Mice, SiS 41). In India, the first independent assessment of the feeding study submitted by Monsanto and its subsidiary Mahyco to the Indian regulatory authorities showed that Bt Brinjal (aubergine) caused many changes in several species of animals including diarrhoea, increased water consumption and decrease in liver weight in rats [21] (Bt Brinjal Unfit for Human Consumption, SiS 41).

There are several reasons why genetic modification is inherently hazardous, as spelt out more than ten years ago [22] (Genetic Engineering: Dream or Nightmare?) and unfortunately, still not taken on board by the regulatory authorities, let alone systematically investigated. The dangers may come from the transgenic protein itself that may be toxic or immunogenic [23] (Transgenic Pea that Made Mice Ill, SiS 29), the toxicity of herbicides such as glyphosate to which more than 70 percent of GM crops now grown globally are made tolerant [24] (Death by Multiple Poisoning, Glyphosate and Roundup, SiS 42) or it could be totally unexpected, unintended effects resulting from the mutagenic insertion of foreign DNA into the genome, and worse, the instability of transgenic lines, which makes proper safety assessment well nigh impossible [25] (Transgenic Lines Unstable hence Illegal and Ineligible for Protection, SiS 38).

One major hazard inherent to GM organisms (GMOs) is enhanced horizontal gene transfer and recombination [26] (Horizontal Gene Transfer from GMOs Does Happen, SiS 39). This is considerably worse with transgenic plants like Golden Rice (both GR1 and GR2) that have been created using the Agrobacterium binary vector system, basically because the Agrobacterium bacteria as well as the binary vector tend to persist in the transgenic plants, providing a ready vehicle for further horizontal gene transfer to all species that interact with the transgenic plant material, including human cells. Agrobacterium is known to invade human cells. Horizontal transfer of transgenic DNA into human cells has the potential to cause harmful mutations including cancer. In general, horizontal transfer of transgenic DNA facilitates the creation of new pathogens. The identification of Agrobacterium sequences in patients with Morgellons’ Disease raises questions as to whether the widespread use of Agrobacterium vectors in genetic modification has indeed resulted in creating a new pathogen for humans [15].

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.”

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