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Synthesis/Regeneration 35   (Fall 2004)



Risky Rice

by Walter Epp




A little-known Sacramento-based company, Ventria Biosciences, tried to get a California permit for commercial cultivation of rice genetically engineered to produce pharmaceutical substances, despite the fact that FDA, EPA, and USDA reviews had not been completed and federal permits had not been obtained. It won narrow approval from the California Rice Commission for an emergency process giving the California Secretary of Agriculture only 10 days to decide, blocking the normal public comment process. The Rice Commission’s lawyer falsely advised them that they could not deny the application; his law firm works for other biotech companies developing GE rice varieties. [1] This would be the first commercialization of a GE pharmaceutical food crop.

Such a precedent-setting decision requires extra diligence.

If it’s so beneficial, why can’t this technology stand the light of deliberate public scrutiny, and why ram it through with such an irregular process?


…why can’t this technology stand the light of deliberate public scrutiny?

Public relations describe the substances produced as extracts from human breast milk and tears, giving a motherhood and apple-pie image, but if the food supply is contaminated, we’ll be dosed with uncontrolled amounts of these pharmaceuticals. Less well known is the possibility that genetic engineering could trigger a genetic meltdown in food species.

A researcher with 30 years experience noted: “Our experiment showed up how imprecise the [genetic engineering] technique is, because we had two GM potatoes, both contained GNA lectin, and both came from the same pot. They were both grown in greenhouses or in fields in tunnels under identical conditions and at the same time. Yet they came out different. The only explanation is that the incorporation of the transgene into the host genome happened at two different places. And the effect on the genome was different.... With our two lines of potato, which should have been substantially equivalent to each other, we found that one of the lines contained 20% less protein than the other. So the two lines were not substantially equivalent to each other. But we also found that these two lines were not substantially equivalent to their parent.” [2]

One obvious corollary of this is that each gene insertion line and each generation of each insertion must be separately tested and approved.

DNA tends to be unstable and prone to recombine. The artificial GE mechanisms enabling insertion of foreign genes also enable them to jump out and re-insert somewhere else, possibly resulting in a cascade of different mutant combinations over multiple generations, each with different properties, including possibly greater toxicity. [3,4,5]

This cascade of genetic rearrangements can stress the organism’s ability to cope. It may take a number of generations for these disruptions to accumulate. If they exceed the organism’s coping mechanisms, the result can be extinction of those populations. [6,7,8,9]

If this instability accumulates quickly, in a small number of generations, it will tend to be self-limiting. If it happens slowly, it may be dwarfed by other factors and limited by natural selection. The worst case is an intermediate rate slow enough that the GE genes and their ensuing instabilities spread through both GE and via cross-pollination to conventional populations, but fast enough to cause them to self-destruct generations later, resulting in extinction of both GE and conventional varieties.

Critical information of paramount importance is how many generations it can take for this process to unfold. For an annual crop like rice, this requires many years. Approval made without knowing this number would be criminally negligent.

Different growing conditions must be tested, as genetic “immune systems,” including genetic mutation repair mechanisms, may be more likely to break down under real-world stresses than controlled laboratory conditions.

If it infected Asia, a genetic meltdown of rice could potentially result in the largest famine in history.

Over 3 billion people eat rice daily. Since the threat of contamination affects them, they must have a say in decisions over GE rice.


Over 3 billion people eat rice daily. Since the threat of contamination affects them, they must have a say in decisions over GE rice.

Advocates say contamination won’t spread, citing rice’s self-pollinating ability and experiments showing pollen drifts only to 10 feet [10], so buffer zones were originally set at only 100 feet.

The California Rice Commission decided buffers should be 100 miles to protect California rice growers. However this neglects to consider that birds can carry rice pollen and seeds long distances.

Bobolinks (also called Ricebirds) pass through California to their winter homes (typically rice fields) in Argentina, Bolivia, Brazil, and Paraguay. [11] Their range has shifted westward, so historical records will likely underestimate their future abundance. [12]

All these countries grow rice. Argentina is negotiating to export rice to South Korea. [13] 100 bird species migrate through Korea, with destinations including Japan and China. [14,15] Thus there’s a route for genetic contamination to go from Southern California to the heartlands of rice cultivation in Asia, even though Southern California is 100 miles away from the nearest commercial rice fields.


…there’s a route for genetic contamination to go from Southern California to the heartlands of rice cultivation in Asia…

Black Terns formerly bred in rice fields as far south as Kern County, so they’re liable to do so again if rice fields reappear. [16]

They pass through Mexico, which grows rice.

Fulvous Whistling-Ducks aren’t common now but were numerous in Southern California when rice was grown there, so they’re liable to return if rice fields reappear. They winter in Cuba, Greater Antilles, and Trinidad, all of which grow rice. [17]

350 bird species travel between California and Central or South America, and/or between Southern and rice-growing Northern California. [18]

Migrant farmworkers can spread seeds and pollen in mud on shoes and clothes.

Rice experts called in when problems arise will also visit conventional rice fields, and could inadvertently spread GE seeds and pollen.

Unexpected floods will wash seeds and pollen downstream into mud which can be picked up by shoes of fishermen or hikers (who could be vacationing conventional rice growers!) and carried to their homes.

Genetically engineered contamination has been widespread in places where planting GE crops was illegal. [19,20] GE Starlink genes turned up in the US food supply despite being illegal for use as food.

A regulatory framework based on the chemical contamination model, where a small amount of contamination has a small effect, is utterly inappropriate and inadequate when dealing with reproducing organisms.

One grain of mutant rice arriving in a rice-growing area could sprout, make pollen and seeds, and then year after year the contamination could spread until it’s pervasive. Scientific experiments have found that a genetically engineered gene was 20 or more times more likely to spread than the same gene induced by mutation. [21]

Genetic contamination has spread over large areas in just a few years. [22,23]

Contamination of food is not the only problem we have to worry about.

GE mechanisms are designed to overcome natural barriers between species, so they are liable to result in unexpected recombinations and transfers of genes among different species. Bacteria are uncontrollable, and different species of bacteria can exchange genetic material through conjugation. Horizontal transfer is believed to be the primary mechanism in the resurgence of antibiotic resistant infectious diseases. GE genes have already been found to move from plant pollen into bacteria. [24,25,26] Thus once pharmaceutical genes get into bacteria they can spread through the environment and be consumed by people. If these bacteria are able to thrive in the gut, they could expose people to substantial doses of the drugs the genes are designed to produce. The substances produced in such conditions may have different toxicity than what was intended. When tryptophan, which is essentially nontoxic, was genetically engineered, differences of only 0.1% in chemical composition due to unexpected interactions resulted in substantial toxicity, including permanent disabilities and deaths. [27]

Actually, Ventria’s GE rice produces substances that are chemically different from human analogs, so they must be tested for allergenicity. [28,29]

Even if identical, substances that help people with some conditions may harm those with other conditions. Lysozyme (one of the substances Ventria’s GE rice is designed to produce) may aggravate pulmonary emphysema. [30] Variant types of lysozyme have been linked to amyloidoses. [31,32]

Lactoferrin (also produced by Ventria’s GE rice) has been implicated as a factor in autoimmune diseases. [33,34] A lactoferrin variant has been implicated in amyloidosis. [35] Lactoferrin has been implicated in a death. [36]

Lactoferrin is an antibiotic. The number of microorganisms in a healthy human digestive system is larger than the number of cells in all the rest of the body, and most of them are beneficial. Killing friendly bacteria can cause disease from higher levels of harmful species. Some say it’s more effective to do the opposite, namely increase beneficial bacteria. [37]


…require companies to post bonds large enough to cover all costs of damage.

While an iron source like lactoferrin may help the iron-deficient [38], it may harm the majority of people. Iron is an oxidant, so it does the opposite of antioxidants which counter free radical damage. [39]

According to the National Institutes of Health, “Iron deficiency is uncommon among adult men and postmenopausal women.

“Iron has a moderate to high potential for toxicity because very little iron is excreted from the body. Thus, iron can accumulate in body tissues and organs when normal storage sites are full…. Accumulation of iron can result in increased production of free radicals.” [40]

Human proteins produced by GE rice may leach from living and decomposing plants into the environment. Indeed, some have proposed collecting products from GE pharmaceutical crops via root exudates. [41,42] Bt protein from GE crops leaches through soil. [43] Proteins from GE rice presumably would do likewise, contaminating water sources and dosing people and animals.

We must ensure companies pay for the consequences of their actions.

One way to do this is require companies to post bonds large enough to cover all costs of damage. Since a reproducing organism could affect hundreds of millions of people for hundreds of years, the size of these bonds would be quite large.

It makes no sense to rush with so many unresolved health, ecological, and economic issues. Rice has been grown for thousands of years; taking several decades to figure out the implications is a prudent minimum time.

The good news is that Ventria’s emergency petition was rejected, and there will be more opportunities for public involvement.

The bad news is that this and other GE products are still in the pipeline, posing threats to food security if not enough people speak up and take action.





Notes:

1. Center for Food Safety May 11, 2004 Press Release, http://www.centerforfoodsafety.org/page312.cfm

2. Dr Arpad Pusztai interview, GM-FREE Vol. 1, no. 3 August/September 1999, http://members.tripod.com/~ngin/pusztai.htm

3. Joe Cummins: GM Crops May All Be Unstable, ISIS Report April 8, 2001, www.i-sis.org.uk/unstable.php

4. Horvath,H, Jensen,L, Wong,O, Kohl,E, Ullrich,S, Cochran,J, Kannangara,C, von Wettstein,D: “Stability of transgene expression, field performance and recombination breeding of transformed barley lines” 2001 Theor Appl Genet 2001,1-11

5. Palevitz,B: “DNA surprise: Monsanto discovers extra sequence in its Roundup Ready soybeans” 2000 The scientist 14,20 (july 24).

6. Joe Cummins: GM Crops May Face Genetic Meltdown, ISIS Report June 12, 2001, www.i-sis.org.uk/meltdown.php

7. Labra M, Savini C, Bracale M, Pelucchi N, Columbo L, Bardini M, Sala F: Genomic changes in transgenic rice plants produced by infecting calli with Agrobacterium tumefacians. 2001 Plant Cell Reports 2001

8. Agrawal G, Yamazaki M, Kobayashi M, Hirochika R, Miyao A, Hirochika H: Screening of rice viviparous mutants generated by endogenous retrotransposon Tos17 insertion tagging of a zeanthin epoxidase4 gene and a novel OsTATC gene. Plant Physiology, 2001, 125, 1248-57

9. Gressel, J: “Molecular biology of weed control” 2000 Transgenic Res 9,355-82.

10. San Luis Obispo Tribune 3/30/2004, http://www.kansascity.com/mld/kansascity/news/8312059.htm

11. Arizona Game and Fish Department Heritage Data Management System: Dolichonyx oryzivorus, www.azgfd.com/w_c/edits/documents/Dolioryz.d.pdf

12. Audubon Society Field Guide to North American Birds, Western Region

13. Oryza Corporation rice market information service, http://oryza.com/news/index.shtml

14. Bird-watching directory, Korean Overseas Information Service, http://www.korea.net/directory/List.asp?Category_id=d00209

15. Wetlands and Birds Korea, http://www.wbkenglish.com

16. Point Reyes Bird Observatory: Black Tern, www.prbo.org/cms/docs/ecol/blte.pdf

17. Arizona Game and Fish Department Heritage Data Management System: Dendrocygna bicolor, www.azgfd.com/w_c/edits/documents/Dendbico.d.pdf

18. Follow the Pacific Flyway in California State Parks, California Department of Parks & Recreation, http://www.parks.ca.gov/?page_id=23379

19. Genetic Modification Taints Corn in Mexico, Carol Kaesuk Yoon, New York Times October 2, 2001

20. Dr. Mae-Wan Ho: "Transgenic Pollution by Horizontal Gene Transfer", http://www.i-sis.org/TransgenicPollution.php

21. J. Bergelson et al., “Promiscuity in transgenic plants,” Nature 395: 25, September 3, 1998

22. Superweeds Invade Farm Fields, Tom Spears, The Ottawa Citizen 6 Feb 2001

23. GM fields spread new superweeds, Jonathan Leake, Sunday Times (London), August 12, 2001

24. Dr. Mae-Wan Ho: Horizontal Gene Transfer, http://www.i-sis.org.uk/horizontal.php

25. Dr. Mae-Wan Ho: Genetic Engineering: Dream or Nightmare, p.18-20

26. Institute of Science in Society News #4 March 2000, www.i-sis.org/i-sisnews4.htm

27. John Fagan: Tryptophan summary, www.psrast.org/jftrypt.htm

28. April 1, 2004 Letter to CDFA Secretary, http://www.organicconsumers.org/ge/riceletter040504.cfm

29. Michael Hansen, Consumer Policy Institute/Consumers Union, City Visions April 12, 2004, http://www.cityvisionsradio.com/archive/040412.htm

30. Cantor,J, Shteyngart,B, Cerreta,J, Turino,G: “The Effect of Lysozyme on Elastase-Mediated Injury”, 2002 Exp Biol Med 227:108-13..

31. Hawkins,P: “Hereditary systemic amyloidosis with renal involvement”, 2003 J. Nephrol 16,443-8

32. Vallelx,S, Drunat,S, Philit,J, Adoue,D, Piette,J, Droz,D, Macgregor,B, Canet,D, Delpech,M, Grateau,G: “Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family”, 2002 Kidney International 61, 907-12

33. Nassberger L, Hultquist R, Sturfelt G: “Occurrence of anti-lactoferrin antibodies in patients with systemic lupus erythematosus, hydralazine-induced lupus, and rheumatoid arthritis,” 1994 Scand J Rheumatol. 23, 206-10

34. Coremans I, Hagen E, Daha M, van der Woude F, van der Voort E, Kleijburgvan der Keur C, Breedveld F: “Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis,” 1992 Arthritis Rheum. 35, 1466-75.

35. Ando,Y: “Analyses of pathogenesis and therapeutic approaches for hereditary amyloidosis”, 2003 Rinsho Byori 51,530-5

36. Tsokos M, Paulsen F: Expression of pulmonary lactoferrin in sudden-onset and slow-onset asthma with fatal outcome, Virchows Arch. 2002 Nov 441(5):494-9

37. Jordan Rubin, Joseph Brasco: Restoring Your Digestive Health, p117, p44, p132-139

38. http://www.ventriabio.com/products/lactoferrin.asp

39. The Antioxidant Activities of Vitamin C and Lipoic Acid in the Body, Jung Suh, Linus Pauling Institute, http://lpi.oregonstate.edu/ss02/suh.html

40. http://www.cc.nih.gov/ccc/supplements/iron.html

41. Hui,Z, Zhang,Z, Bao,Y, Liu,W, Gan,Q, An,L: “Production of functional single chain Fv protein in transgenic tobacco root exudates” 2002 Biotechnology Letters, 24, 1531-34

42. Borisjuk,N, Borisjuk,L, Sithes,L, Petersen,F, Gleba,Y, Raskin,I: “Production of recombinant proteins in plant root exudates” 1999 Nature Biotech 17, 466-71

43. Saxena,D, Flores,S and Stotzky,G: “Vertical movement in soil of insecticidal Cry 1Ab protein from Bacillus thuringinesis” 2002 Soil Biology and Biochemistry 34, 111-20






[17 aug 04]


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