Golden Rice and Hazards of GMOs

Dr. Mae-Wan Ho. Lecture at Workshop on Hazards of GMOs, Food and Democracy, 5^th European Conference on GMO-Free Regions, 25 April 2009, Cultural and Conference Centre Lucerne (KKL), Switzerland

Download the accompanying presentation to this lecture here

Thank you for inviting me here. I am Director of the Institute of Science in Society (ISIS). Our mission is to provide accessible and critical scientific information to the public and policy makers on a wide range of topics, genetic engineering, climate change, renewable energies, sustainable agriculture, and so on, in a bid to reclaim science for the public good, which is very important as corporations are increasingly monopolising not just seeds and food but scientific knowledge [1] (Corporate Monopoly of Science  SiS 42).  The ‘public’ includes also scientists trying to understand work done in other disciplines, which is not easy. We are fortunate to have scientists, Peter Saunders and myself, and Joe Cummins, who are polymaths to varying degrees. The ISIS website www.i-sis.org.uk contains many useful resources, and we publish a colourful, beautifully illustrated quarterly magazine, Science in Society.

I first spoke out against GMOs in 1994, when the Third World Network (TWN) (www.twnside.org.sg) asked me to advice on genetic engineering. It was a desperate situation when almost everyone who knew anything about genetic engineering was involved in exploiting it commercially, and safety was simply not an issue. Worse yet, scientists who spoke up for it were vilified and victimised. I want to pay special tribute to Arpad Pusztai, who is in hospital recovering from a stroke. It was Arpad who really alerted the public to the potential hazards of GMOs by telling them the truth about his experiments.

Very soon after working with TWN, I realised that the lack of independent, reliable, and accessible scientific information was much larger than just genetic engineering. That was why my husband Peter Saunders and I co-founded ISIS in 1999. Reliable and independent scientific information is crucial for democracy, not just for food, but right across the board for health, energy, and decisions on science policies that affect our everyday life and that of our children and grandchildren.

The return of Golden Rice

I want to use Golden Rice as the jump off point to talk about the hazards of GMOs, because Golden Rice is presented as the flagship product of the industry, the beneficent, ethical and acceptable face of GMOs; its hazards, therefore, are all the more insidious and dangerous.

Golden Rice was created 10 years ago as a public relations exercise for the biotech industry that was failing to convince people to accept GMOs. Ingo Potrykus appeared on the cover of Time magazine (7 August 2000), with the headline: “This Rice could save a million kids a year” (from blindness due to vitamin A deficiency). The rice was genetically engineered to produce pro-vitamin A or b-carotene. The ploy was thoroughly exposed in our ISIS report [2] (see The 'Golden Rice', An Exercise in How Not to Do Science, ISIS Report), by Greenpeace, and others. But Golden Rice did not go away.

Last year, it staged a come back with a special feature in Science journal [3], “Tough lessons from Golden Rice”. And it transpired that Tufts University in Boston, United States, has been carrying out ‘clinical trials’ of Golden Rice on children. More than 30 senior scientists and academics signed an open letter condemning the work [4] (Scientists Protest Unethical Clinical Trials of GM Golden Rice). The trials were in breach of the Nuremberg Code of Ethics brought in at the end of the Second World War to prevent repetition of experiments conducted by Nazi scientists including many on children.

Clinical trials on children expose the inadequacies of the regulatory regime

Of the three clinical studies listed on the US clinical Trials website, two involved children 6-10 years old, to compare the vitamin A value of the b-carotene in oil capsule, spinach and Golden Rice. The third was on 6 adults 40-70 years of age. These trials were carried out at different times between 2004 and 2009. None registered any results whatsoever. Although WHO succeeded in making it mandatory to register clinical trials, that did not extend to reporting the results.

What’s more, the Golden Rice in the trials (GR2) was not one identifiable variety. Instead, it was an experimental collection of transgenic events still in the laboratory [5] (The Golden Rice Scandal Unfolds, SiS 42), not characterised in terms of basic molecular genetics or biological and biochemical properties, not tested pre-clinically on animals, or subjected to any other safety assessment.

That they have been approved for clinical trails on the most vulnerable shows just how inadequate the regulation of GMOs is in the United States, and any other country that follows that same model. The Americans not only depend on the biotech companies to do safety assessment, and regulation is entirely voluntary. They also routinely waive even that on grounds that the GMO is “generally regarded as safe” or GRAS for short.

In the case of so-called nutritionally enhanced plants such as Golden Rice, it will most likely have no requirement for safety testing at all, as Dave Schubert at the Salk Institute for Biological Sciences in La Jolla California, points out [6]. And that in itself raises serious safety concerns.

The registered clinical trials were not the only ones. The Golden Rice Project website [7] (accessed 21 April 2009), which claims unjustifiably that “Golden Rice has been researched thoroughly”, lists 9 tests that included tests for b-carotene bioavailability and bioconversion to retinol with deuterium-labelled Golden Rice fed to adults in USA and a small group of children in China; also feeding trials with human adults in China to measure the effect of fat in the diet on bioconversion and bioavailability. Again, no results were posted.

Golden Rice was never ready for commercial approval

Although Golden Rice was created by Ingo Potrykus at the Institute of Plant Sciences in the Swiss Federal Institute of Technology and Peter Beyer at the University of Freiburg some ten years ago [8], it has remained in the lab since. Speaking to Science journal in April 2008 [6], Potrykus bitterly blamed “2 decades of fear-mongering by organizations such as Greenpeace” that has created a regulatory climate so burdensome that only big companies can afford to get any GM products approved. Closer to the truth may be that the product was never ready for commercial approval.

According to a recent report commissioned by foodwatch in Germany [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 cooking, 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 in the original GR1. GR2 produced up to 23 times the amount of carotenoids in 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 technology is so uncontrollable that each event from a single experiment using the same materials will result in a completely different variety with unpredictable properties (which is why Europe requires ‘event specific characterisation’). The results of the clinical trials, as yet undisclosed, could well be utterly worthless.

A GM Trojan Horse in the guise of a Humanitarian Project

Syngenta had donated the 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”, such as “being governed by the strategic direction of the Golden Rice Humanitarian Board”, which as it turns out, includes clinical trials on children. 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 made less tha US$10 000 could get it for free. Dubock retired from Syngenta in 2007, but remains a member of the Golden Rice Humanitarian Board, chaired by Potrykus.

Golden Rice has all the trappings of a Trojan Horse to get GM rice widely to Third World countries. It is being hybridised with local varieties [7], in a bid to contaminate and jeopardize the major rice producers and consumers of the world, which include the poorest, most vulnerable nations.

Golden Rice, an exercise in how not to do science

Golden Rice  had already cost US$100 million in public money, and was tied up in at least 70 patent on genes, sequences, and constructs; a problem only partly solved in the “ground-breaking deal” worked out by Dubock (see above)..

As pointed out then and now, there are infinitely cheaper sources of vitamin A or pro-Vitamin A such as carrots and certain green vegetables, which would be rich in other essential vitamins and minerals, and hence much more nutritious [2, 6, 11].

The main cause of hunger and malnutrition in the Third World is the industrial monoculture 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 being promoted in the so-called “Doubly Green Revolution” is industrial monoculture, only worse, and will exacerbate this trend [12] (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 [1]. 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. I have highlighted the special hazards of the Agrobacterium vector system since 2003 [12] (Agrobacterium & Morgellons Disease, A GM Connection?, SiS 38) (more later)

A detailed audit on the project [2], and I think this should be done for all scientific projects, uncovered fundamental flaws from the scientific and social rationale to the science and technology involved. 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 [14] (GM Food Nightmare Unfolding in the Regulatory Sham, ISIS scientific publication).The situation is that whenever and wherever feeding trials are carried out independently of the biotech industry, health impacts are found. And this applies to re-analysis of the raw data in experiments carried out by the biotech industry, as Giles-Eric Seralini has highlighted in his talk.

ISIS called for a moratorium in 1999 and in 2003, a global ban on environmental releases and a comprehensive shift to non-GM sustainable agriculture [15] (The Case for A GM-Free Sustainable World, Independent Science Panel Report, ISIS Publication).

There is indeed 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, sterility and death, raising the distinct possibility that genetic modification is inherently dangerous [16] (GM is Dangerous and Futile, SiS 40). We have accumulated a big dossier of the problems and hazards of GMOs, including socioeconomic impacts [17] GM Science Exposed: Hazards Ignored, Fraud, Regulatory Sham, Violation of Farmers Rights (ISIS CD book). 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 [18] (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 [19] (GM Maize Disturbs Immune System of Young and Old Mice, SiS 41). In India, the first independent assessment carried out by Giles-Eric Seralini of CRIIGEN (France) 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 decreased liver weight in rats [20] (Bt Brinjal Unfit for Human Consumption, SiS 41)

There are several reasons why genetic modification is inherently hazardous, as spelt out in my book [21] (Genetic Engineering: Dream or Nightmare?) first published more than ten years ago, and unfortunately, still not taken on board by the regulatory authorities, let alone systematically investigated, though many of the predictions have come to pass.

I mentioned that the dangers might come from the transgenic protein itself, as subsequently shown when a harmless protein transferred from bean to pea caused severe inflammation in the lungs of mice and generalised food sensitivity [22] (Transgenic Pea that Made Mice Ill, SiS 29). I stressed the toxicity of herbicides; and indeed, glyphosate to which more than 80 percent of GM crops now grown globally are made tolerant [23], has since been found to be highly toxic to human placenta and embryonic cells (Death by Multiple Poisoning, Glyphosate and Roundup, SiS 42). I drew attention to 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 [24] (Transgenic Lines Unstable hence Illegal and Ineligible for Protection, SiS 38). By the way, this is also the best challenge to patents on life, as there is no scientific basis for patent protection whatsoever.

Transgenic lines are unstable, basically because the constructs are artificial combinations of sequences that never existed in billions of years of evolution with extra weak joints (recombination hotspots). The constructs are equipped with sticky ends (also recombination hotspots) designed to invade genomes. They insert randomly, though much more likely into regions with active genes, causing major disruption. Once inserted, they may not stay put, but can rearrange, jump to another location in the host genome, or else into the genome of a cell from a different species (see [25] Living with the Fluid Genome, ISIS publication). 

One major hazard inherent to GM organisms (GMOs) that I have highlighted is enhanced horizontal gene transfer and recombination [26], and this has been corroborated (Horizontal Gene Transfer from GMOs Does Happen, SiS 39). Horizontal gene transfer 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. This was known for a long time, in research commissioned by the British government, but has been swept under the carpet. I have tried to chase up the sequel with the Department for the Environment, Food and Rural Affairs (DEFRA) without success. Agrobacterium is known to share regulatory factors required for conjugation (gene exchange) between bacteria; and to invade human cells. In general, horizontal transfer of transgenic DNA facilitates the creation of new pathogens. Horizontal transfer of transgenic DNA into human cells has the potential to cause harmful mutations including cancer. 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 resulted in creating a new pathogen for humans [16]. We have sent our report to the Centers for Disease Control in the United States, which had announced it would investigate the cause of Morgellons Disease after years of denying it exists.

Golden Rice particularly dangerous

A good, health-promoting diet requires a balance of different nutrients as well as vitamins and minerals. The unbalanced enhancement of single nutrients, as in ‘nutritionally enhanced’ GM crops may do more harm than good [27] (GM Crops and Microbes for Health or Public Health Hazards?  SiS 32). As David Schubert points out [6], plant enzymes have very low substrate specificity, which are unpredictably altered by mutations and gene interaction effects associated with GM technology. One metabolite of b-carotene enhanced in Golden Rice is retinoic acid (RA). RA is biologically active at very low concentrations. Schubert states that [6] “excess RA or RA derivatives are exceedingly dangerous, particularly to infants and during pregnancy.”

Six hundred naturally occurring compounds exist in the carotene family, and at least 60 can be precursors to retinoids. While all retinoids and derivatives are likely to be teratogenic, only three: retinol, RA, and retinal are sufficiently known and can be measured. Therefore, at the very least [6], “extensive safety testing should be required before the introduction of golden rice as a food.”

GM science is obsolete, we need organic localised agriculture & food systems now

We should ban the environmental releases of GMOs decisively now. The greatest danger from GMOs is that genetic modification was inspired by the old genetic determinist paradigm, already superseded by the new genetics of the fluid genome [25] almost as soon as genetic modification began in the late 1970s. And there have been plenty of indications that the technology simply does not work well, apart from anything else.

In March this year, South African farmers suffered massive losses when 82 000 ha of GM maize failed to produce hardly any seeds (MON810, Nk603 and hybrids thereof). [28], possibly the result of genome instability that continues to dog transgenic varieties [23]. Not only have GM crops failed, at times catastrophically. They are not safe, and the harm is not restricted to a single generation.

Geneticists are documenting how toxic substances affect not just the individuals exposed, but also their children and children’s children [29] (Epigenetic Inheritance - What Genes Remember, SiS 41), basically because the substances mark and determine how certain genes are expressed, and the effects become inherited [30] (Epigenetic Toxicology, SiS 41). That’s why risk assessment of GMOs and other xenobiotics have to be carried out over three or four generations. Decades of sequencing and dissecting the human genome have confirmed that the real causes of ill health are environmental and social [31] (From Genomics to Epigenomics, SiS 41). It is not the genetic messages encoded in genomic DNA, but environmentally induced epigenetic modifications that overwhelmingly determine people’s health and wellbeing. Early nutrition and parental care play a large role [32] (Caring Mothers Strike Fatal Blow against Genetic Determinism, SiS 41) in an individual’s physical and mental health.

Europe’s agricultural policies must support and promote organic, localised and biodiverse agriculture that is the most effective way to deliver health, wealth, and happiness to the world’s nations, as shown in the ISIS report [33]  Food Futures Now: *Organic *Sustainable *Fossil Fuel Free.

Download the accompanying presentation to this lecture here

Article first published 29/04/09

---

References

1. Saunders PT. Corporate monopoly of science. Science in Society 42 (in press).
2. Ho MW. The ‘Golden Rice’ – An Exercise in How Not to Do Science. TWN Biotechnology and Biosafety Series No. 6, Third World Network, Penang, 2002. https://www.i-sis.org.uk/onlinestore/books.php
3. Enserink M. Tough lessons from Golden Rice. Science 2008, 320, 468-71.
4. Scientists Protest Unethical Clinical Trials of GM Golden Rice, Open Letter, 12 February 2009, for complete list of signatories see http://www.gmfreecymru.org/open_letters/Open_letter12Feb2009.html)
5. Ho MW and Cummins J. The Golden Rice scandal unfolds. Science in Society 42 (to appear).
6. Schubert DR. The problem with nutritionally enhanced plants. J Medicinal Food 2008, 11, 601-5.
7. Research on Biosafety, http://www.goldenrice.org/Content2-How/how3_biosafety.html
8. Ye X, Al-Babili S, Kloti A., Zhang J, Lucca P, Beyer P. and Potrykus I. Engineering the provitamin A (b-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. Science 2000, 287, 303-5.
9. Then C. A critical look at golden Rice after nearly 10 years of development. C Commissioned by Foodwatch in Germany, January 2009.
10. Paine JA, Shipton CA, Chaggar S, Howells RM, Kennedy MJ, Vernon G, Wright SY, hinchliffe E, Adams JL, Silverstone AL and Drake R. Improving the nutritioinal value of Golden Rice through increased pro-vitamin A content. Nature biotechnology 2005, 21, 482-7.
11. Koechlin F. The ‘golden rice’ – a big illusion? Third World Resurgence 2000, #114/115, 33-35.
12. Ho MW. Beware the new “doubly Green Revolution”. Science in Society 37, 26-29, 2008.
13. Ho MW and Cummins J. Agrobacterium & Morgellons Disease, a GM connection? Science in Society 38, 33-35, 2008.
14. Ho MW, Cummins J and Saunders PT. GM food nightmare unfolding in the regulatory sham. Microbial Ecology in Health and Disease 2007, Disease 2007, 19, 66-77. https://www.i-sis.org.uk/onlinestore/papers2.php#section5
15. Ho MW and Lim LC. The Case for a GM-Free Sustainable World, Independent Science Panel Report, Institute of Science in Society and Third World Network, London and Penang, 2003; republished GM-Free, Exposing the Hazards of Biotechnology to Ensure the Integrity of Our Food Supply, Vitalhealth Publishing, Ridgefield, Ct., 2004 (both available from ISIS online bookstore  https://www.i-sis.org.uk/onlinestore/books.php#1)
16. Ho MW. GM is dangerous and futile, we need organic sustainable food and energy systems now. Science in Society 40, 4-8, 2008.
17. GM Science Exposed: Hazards Ignored, Fraud, Regulatory Sham and Violation of Farmers’ Rights, ISIS CD book, 2009.
18. Ho MW. GM maize reduces fertility & deregulates genes in mice. Science in Society 41, 40-41, 2009.
19. Ho MW. GM maize disturbs immune system of young and old mice. Science in Society 41, 42, 2009.
20. Burcher S. Bt brinjal unfit for human consumption. Science in Society 41, 50-51, 2009.
21. Ho MW. Genetic Engineering Dream of Nightmare? The Brave New World of Bad Science and Big Business, Third World Network, Gateway Books, MacMillan, Continuum, Penang, Malaysia, Bath, UK, Dublin, Ireland, New York, USA, 1998, 1999, 2007 (reprint with extended Introduction). https://www.i-sis.org.uk/onlinestore/books.php
22. Ho MW. Transgenic pea that made mice ill. Science in Society 29, 28-29, 2006.
23. Ho MW and Cherry B. Death by multiple poisoning, glyphosate and Roundup. Science in Society 42 (to appear).
24. Ho MW. Transgenic lines unstable hence illegal and ineligible for protection. Science in Society 39, 28-29, 2008.
25. Ho MW. Living with the Fluid Genome, ISIS TWN, London, 2003.
26. Ho MW and Cummins J. Horizontal gene transfer from GMOs does happen. Science in Society 39, 22-24, 2008.
27. Cummins J and Ho MW. GM crops and microbes for health or public health hazards?
28. “Monsanto GM-corn harvest fails massively in South African”, Adriana Stuit, 29 March 2009, http://www.digitaljournal.com/article/270101
29. Ho WM. Epigenetic inheritance, “what genes remember”. Science in Society 41, 4-5, 2009
30. Ho MW. Epigenetic toxicology. Science in Society 41, 12-15, 2009.
31. Ho MW. From genomics to epigenomics. Science in Society 41, 10-12, 2009.
32. Ho MW. Caring mothers strike fatal blow against genetic determinism. Science in Society 41, 6-9, 2009.
33. Ho MW, Burcher S, Lim LC, et al. Food Futures Now, Organic, Sustainable, Fossil Fuel Free, ISIS TWN, London, 2008. https://www.i-sis.org.uk/foodFutures.php