Spilling the Beans, June 2006 (sent early July 2006)

Action Step: Ask the plum industry to help stop the USDA's planned introduction of genetically modified (GM) plums.

Dear Readers,

After reading this article, I ask you to take a moment to send a friendly note to the plum industry, asking them to help stop the pending introduction of GM plums. Since the article is a bit long, if you put off reading it for now, please don’t put off helping with this important action alert. The food industry has successfully stopped several GM crop introductions. I believe that if the companies that grow and sell plums urge the USDA to withdraw the plum application, it will be withdrawn. There is a short window. (The USDA comment period ends July 17, but comments made after that BY THE INDUSTRY may still be effective.) To help, please click here.
http://www.responsibletechnology.org/GMFree/TakeAction/PlumIndustryEmail/index.cfm

Regards,
Jeffrey Smith

Disease-resistant genetically engineered crops may make humans (and plants) more vulnerable to viruses
By Jeffrey Smith

The US Department of Agriculture wants to introduce a new variety of plum, genetically modified (GM) to resist the plum pox virus. Disease-resistant crops comprise less than one percent of the acreage devoted to GM varieties worldwide, but occupy a much bigger portion in biotech promotional literature. That’s because engineering a crop to resist disease sounds more appealing than inserting a gene to make a crop produce its own pesticide or withstand herbicide””the two traits that make up the other 99 percent of today’s GM world.

There are three commercialized virus-resistant GM varieties: zucchini, crookneck squash and the only commercialized GM fruit, papaya. GM papaya grows solely in Hawaii and was introduced in 1998 to protect the crop from the devastating ring-spot virus. But according to a May 2006 report by Greenpeace, the GM papaya turned out to be "more devastating than the virus. "Upon introduction, the selling price for the papaya crashed from $1.23 per kilo to $0.89, after "traditional buyers of Hawaiian papayas, such as Japan and Canada, rejected [it]." Now, if Hawaiian papaya growers want to sell to Japan, they have to pay extra for segregating and testing their papayas to make sure they are non-GM. The Japanese market shrunk from $10.3 million in 1998 to $4.6 million in 2005. Although Canada started accepting GM papayas in 2003, the price didn’t recover. In the 2004 and 2005 growing seasons, the selling price "averaged less than $0.80 per kilo, at or only marginally above the production cost for many farmers." [1] While business is booming in other papaya growing regions, Hawaiian production is at its lowest point in more than a generation.

This hasn’t stopped the USDA from trying to gift the plum industry with a virus-resistant catastrophe of its own. And this in spite of the fact that the plum pox virus is not even a current threat. According to Steve Poe, Senior Operations Officer who coordinates the USDA's program to wipe out the virus (using non-GM methods), "We’re on the tail end of eradicating this thing." The incidence of the disease is down to about 1 tree per year, he says.

But there is a current threat that the USDA and other agencies have continued to disregard: The virus-resistant crops already on the market may be increasing the susceptibility of consumers to viral infections and, ironically, even putting the crops at greater risk. According to virologist Jonathan Latham of the Bioscience Resource Project, "None of the important questions about the safety of viral transgenes have been answered. We still have no idea whether they will cause the evolution of new viruses by recombination or what will be the effect of putting viral proteins into plants."

Virus-protection through gene silencing

Although some viruses are DNA-based, most plant viruses exist as RNA strands. Normally, when an RNA virus attacks a cell, it will produce enormous number of copies of itself. The copies, in turn, produce viral protein, which can help to disable the cells defenses to the virus.

Plants have developed a gene silencing mechanism to defend against this onslaught. After the cell recognizes an RNA virus, the double stranded RNA (dsRNA) is cut into short pieces and stripped into a single strand. That strand is used as a reference to "find" other RNA with identical or similar sequences, which are then destroyed or degraded.

Each viral resistant GM crop is designed to protect against a specific RNA virus. First, scientists identify a piece of RNA from the "target" virus, and then build a piece of DNA””a transgene””with a sequence designed to create the viral RNA. The transgene is inserted into the genome of a plant cell, which in turn is grown into a plant. In every cell of that plant and its offspring, the inserted transgene is "transcribed" into viral RNA. Thus, it arms the gene silencing mechanism to be on the lookout for the target virus. The RNA may also produce viral proteins in every cell.

Thus, there are four components of a virus-resistant GM plant that must be considered when looking at the possible effects on humans.
The viral protein
The RNA
The inserted gene (transgene)
Any changes in the plant due to the insertion process Each carry unique risks.

Viral proteins can increase susceptibility to viral infections

As described above, viruses produce proteins that attack and disable the plant cells’ defenses, increasing the chances that the virus will thrive. More than 100 studies have shown, however, that the proteins created by one virus can promote infections by other related and unrelated viruses.[2]'[3]

The viral proteins that function in plants may similarly disable viral defenses in humans, because important mechanisms that defend against viral attack are quite similar in plants and animals. Thus, consuming GM crops that make viral proteins in every cell may weaken our resistance to viruses. This may be particularly true in the gut””where viral proteins would circulate after a meal and which is an important entry point for viral infections. Since we do not fully understand all the ways in which plant viruses overcome host defenses and we do not know which viral proteins are involved, we cannot identify in advance which viral transgenes are likely to be hazardous.

Viral proteins may be toxic

In addition to attacking viral defenses, viral proteins can also be toxic. They attack fundamental processes, such as the cycle by which a cell divides and the mechanism for creating proteins from RNA.[4] If these were damaged in human beings, it could have serious health consequences. (Disrupting the cell cycle, for example, can lead to cancer.)

Since these fundamental metabolic activities are similar in plants and humans, a toxic viral protein that attacks them in crops might similarly attack that process in people. Viral proteins from one kingdom have in fact been shown to be toxic to organisms from other kingdoms. Plant viral proteins can affect yeast, for example, and some human viral proteins can disrupt plants. According to Latham, "There is no good reason why it should not happen the other way round."

In some cases, if a GM viral protein disrupts plant metabolism, it would be obvious to plant breeders and the variety would not be commercialized. This would not always be the case, however. Humans may be more sensitive than plants to the effects of the viral proteins. Also, in some cases, the quantity of viral protein that is produced in a GM plant can be significantly increased. According to Latham, the proteins produced in GM crops have not been properly evaluated for toxicity in humans.

RNA may be hazardous

According to Nature, RNA molecules are "now known to be vital in controlling many cellular processes in plants and animals."[4],[5] In fact, "well over one-third of human genes appear to be" regulated by double stranded RNA (dsRNA).[6] RNA also appears to be passed on to future generations””a characteristic previously thought to be the exclusive domain of DNA. Studies indicate that RNA inherited from parents silenced a gene in mice[7]and repaired an abnormal DNA sequence in a plant.[8]

According to the Centre for Integrated Research on Biosafety (INBI), "Once introduced into a model plant or animal, the effect of dsRNA is systemically spread throughout the organism and persists through the entire developmental period."[9]Not only can RNA effects be transmitted through food, in many different organisms that effect can be inherited by the next generation (although this has not been demonstrated for humans).[10]For example, when worms were fed bacteria engineered to produce dsRNA, the dsRNA survived the digestion in the worms’ gut and penetrated into the gut cells and deeper tissues. It silenced the corresponding gene in the worm and in the offspring for at least two generations.[11] "The same dsRNA can have physiologically different effects at different concentrations,[12],[13] and it is not always clear in advance which gene the dsRNA will impact.

Regulators have dismissed concerns that novel RNA sequences from GM crops may be hazardous. When, for example, INBI raised the issue to Food Standards Australia New Zealand (FSANZ) in regard to a GM corn (that was not virus-resistant), FSANZ claimed that "RNA is rapidly degraded," and unlikely to survive digestion, enter human cells, or exert an effect. INBI had to update FSANZ’s obsolete argument. INBI pointed out that dsRNAs "are stable enough in mammalian cells to be routinely used as gene regulators." They cited recent studies demonstrating that dsRNA "is transmitted through food in other animals, where it survives degradation" and impacts gene expression. [14]

For virus-resistant GM crops that are specifically engineered to create small regulatory dsRNA, regulators are similarly dismissive. They claim that people have eaten virus-infected food for a long time, so it must be safe. This was the position of the US panel that looked at the GM plums. While their theoretical argument may sound strong, like many assumptions used as the basis for GM crop approvals, it lacks experimental verification. Given the significant potential for harm if the assumption is wrong, it is irresponsible not to test.

Even the argument on its own, however, is flawed. "In truth it is a half argument," says Latham. "The other half requires reliable evidence that people who ate the virus-infected crops were absolutely fine in every way." He says that "an experiment is only as good as its controls, but in this ‘experiment’ there were none, because no one was found who hadn’t eaten viruses."

If the natural RNA did turn out to be safe, the transgenic version might still be dangerous. The two versions of RNA are not identical and interchangeable. The naturally occurring sequence of a gene is usually altered by scientists prior to insertion. In addition, the process of insertion can cause the gene to become truncated, mutated or littered with extraneous fragments. Other studies suggest that the transgene may rearrange spontaneously in subsequent growing seasons.[15] A 2005 study also demonstrated that the transgene in GM soybeans don’t create RNA as they were designed to. The authors suggest that other GM crops may also produce unnatural, unintended RNA combinations.[16]

According to geneticist Joe Cummins, "The fact that people may have eaten virus infected plums does not really indicate that the transgenic plum that resists virus infection in a novel way is safe for people." He says, "It is not unreasonable to suggest that a unique interfering plum RNA may be active in humans and animals." Cummins says that "common sense requires adequate safety experiments," and he calls for "fuller testing of the small silencing RNA from the transgenic plum."[17] INBI similarly cautions regulators against dismissing the risks of RNA based on unproven assumptions. They say that testing potential health impacts of RNA from GM crops on humans, which has not been done for any GM crops thus far, is "imperative."[18]

Shifting an RNA virus onto DNA may have dangerous, long-term consequences

Until the introduction of virus-resistant GM crops, their target viruses existed exclusively as RNA-based organisms. When scientists create a viral transgene, however, they introduce an entirely new DNA version. According to Latham, this carries a potential risk that is not generally acknowledged. "The virus is available for recombination with a totally new spectrum of organisms," he warns. "The danger would become especially important if the transgenic protein were useful to the organism that picked it up."

Consider, for example, the possibility that viral transgenes might transfer into the DNA of gut microorganisms. This type of "horizontal gene transfer" from GM food to gut bacteria was confirmed in the case of Roundup Ready soybeans. That was the only human feeding study ever conducted on GM food. No such test has been carried out using virus-resistant crops, but transfer of viral transgenes is certainly plausible. Once transferred, our own bacteria may produce viral proteins inside our intestines over the long term, potentially weakening our defenses against viral infection and attacking fundamental metabolic processes.

[Note: During the development of the GM plum, the same viral transgene was inserted into many different plum cells. Although GM plums created from these other experimental insertions produced viral protein, the transgenic plum under review by the USDA, "Honey Sweet," produces little or no viral protein. While this reduces risks somewhat, if the viral RNA transfers into other viruses or the viral DNA ends up in gut bacteria, they may begin producing potentially harmful viral protein in that new organism. This needs to be studied.]

Viral genes may create new harmful plant viruses

In addition to posing risks for humans, virus-resistant GM crops might increase the likelihood for new viruses to attack the plant. One way for this to occur is through the action of viral proteins. As mentioned above, proteins produced from one virus may attack the host cells’ defenses, making it more susceptible to other viruses. In fact in one study, proteins from viral transgenes allowed a plant to become infected with an insect virus, not normally found in plants.[19]

One type of protein produced by viruses is called a coat protein. It surrounds (encapsidates) the RNA, protecting it from being broken down by threats such as ultra violet light or enzymes. It is possible for a coat protein form one virus to encapsidate another virus. This would make it possible for that new virus to be picked up by an insect and transported to other plants. The risk of encapsidating the wrong virus (transcapsidation) is not a unique risk of GM plants, but the presence of coat protein produced in every cell of the plant can increase the probability that it will occur.

Another concern about GM crops is that inserted viral genes can come into proximity with related and unrelated natural viruses and recombine to create new versions. These new "offspring" viruses can be quite different from either "parent." Many reports specifically demonstrate that natural viruses do recombine with the viral sequences inserted into GM plants,[20] including the viral transgene used in plums.[21] "In some cases recombination occurred at very high rates-in up to 80%[22] of all plants tested."[23] According to Latham, experiments suggest that recombination between viral transgenes in the currently commercialized GM crops and naturally occurring viruses are inevitable. The consequences of the recombination, however, are unpredictable.

Of particular concern is that the viral genes will transfer to viruses that do not normally infect the plant.[24] The invading virus, which is not adapted to that plant, would acquire a transgene that is adapted, thereby making it more likely to attack that plant.[25] It is ironic that GM crops designed to resist one virus "may be especially susceptible to new infectious viral diseases."[26]

Diseased plants may impact human health

If GM plants do generate new plant viruses, this has several implications for human health:

The infected plants create viral proteins. As discussed, these may increase our susceptibility to viral infection or be toxic.

If plants develop novel viruses, it is likely that they will be treated with pesticides, which increases human health risks.

Plants that are infected by viruses may have altered levels of anti-nutrients, toxins, and allergens, and may be more susceptible to mold infestation. All of these may affect the health of the consumer.

It is important to note that the key concern about creating new viruses is related to plant viruses, not human viruses. Natural barriers tend to block a virus in one kingdom from attacking organisms in another kingdom. Therefore, the tendency to create new viruses in plants does not mean that they will attack humans. On the other hand, as mentioned above, when genes from two distinct viruses were inserted separately into a plant, the two viral proteins made the plant susceptible to infection by an animal (insect) virus. There are also other examples of cross kingdom viral adaptations.[27] So in theory, the use of transgenic viral genes may increase the probability that a plant can carry a virus that will function in humans. As there is little or no research on this, the risk remains speculative.

Generic risks from GM plants

While most of the concerns raised thus far relate to disease-resistant GM crops, all GM varieties carry generic risks. The process of creating a GM crop typically causes significant mutations and altered gene expressions throughout the genome, with the possible creation of toxins, allergens, carcinogens and anti-nutrients. The transgene may rearrange during insertion or perhaps at a later time, producing proteins that were never intended or tested. All these uncontrolled and unpredicted changes within the DNA also provide opportunities for creating RNA sequences that might have negative impacts. According to INBI, the potential for gene insertion to create regulatory RNA "is too high by chance to ignore."[28]

In addition, the genetic material that is inserted with the transgene””the promoter, antibiotic resistant marker and terminator””all carry significant risks that have not been properly studied. And many of the safety-related assumptions about these elements that were initially proclaimed by the biotech industry have since been overturned.

Responding to the threat

The FDA has no required safety studies for GM crops and the USDA continues to quote outdated theories (see side bar below for some examples). These actions are consistent, however, with the fact that US regulatory agencies are officially charged with the responsibility to promote the biotechnology industry. Originally, politicians claimed this effort would increase US exports. Now that worldwide rejection of GM crops has actually shrunk US corn and soy exports, for example, to the point of requiring an extra $2-3 billion per year in price supports, promotion of biotech appears to be more about appeasing a powerful corporate lobby.

Although consumers’ concerns about GM foods are not always heeded by governments, the food industry has been more responsive. Their concern about potential loss of markets has had a significant impact in reigning in biotech expansion. When Monsanto tried to introduce their GM wheat, an Iowa State University economist projected a loss of 30-50 percent of the US foreign wheat sales and drop in prices by about a third.[29] The wheat industry lobbied hard for North America to be a GM-wheat-free-zone and Monsanto withdrew its application.[30] When Hawaii coffee growers realized that GM coffee might destroy its premium market, it successfully appealed to the University of Hawaii not to develop any GM varieties. GM flax was taken off the market in 2001 due to pressure from the Flax Council of Canada and the Saskatchewan Flax Development Commission.[31] GM sugar beets were rejected by U.S. sugar refiners.[32] And warnings from rice millers and others halted the commercialization of GM rice.[33]

Now it’s time for the plum producers to protect their markets. The US is the third leading plum exporter. California grows the vast majority, with more than $130 million worth grown in 2002. The plum pox virus, which had infected trees in Pennsylvania, is not even a West Coast phenomenon. But if GM plums are introduced anywhere in the US, market rejection will surely be an issue, as will contamination, rejected shipments and extra costs for segregation and testing.

If you wish to give friendly encouragement to the plum and prune industry to ask for the USDA to stop the GM plum, please go to www.responsibletechnology.org. In this case, it won’t require that Monsanto or another biotech company withdraw their application. The GM plums were developed and promoted by the USDA itself.

As for the other virus-resistant crops, Hawaiian GM papayas are shipped to Canada and a few cities on the West Coast, such as Los Angeles and San Francisco. To avoid it in those locations, inquire about the source of the fruit (and recommend to vendors to avoid it as well.) Unfortunately, organic and non-GM conventional papaya from Hawaii are easily contaminated by GM varieties. Cross-pollination of a non-GM papaya tree can make the seeds GM, while the flesh of the fruit remains non-GM. Consequently, some organic growers planted the seeds of "organic" papaya, only to discover that their orchard was entirely GM. Similarly, those buying papaya at the market may throw the seeds on the ground or plant them in their garden, inadvertently spreading the GM variety. In a study in 2004, "nearly 20,000 papaya seeds from across the Big Island, 80% of which came from organic farms and the rest from backyard gardens or wild trees, showed a GM contamination level of 50%."[34] The GM plum under review can likewise turn the seeds of neighboring trees into GM varieties.

The virus-resistant GM Zucchini and crookneck squash varieties are mixed in low quantities with conventional brands in the US. To avoid them, it may be easiest to buy organic, which has probably suffered minimal contamination. As for the four major GM crops, soy, corn, cottonseed and canola, go to www.seedsofdeception.com to learn how to avoid them when shopping or in restaurants.

Safe eating.

SIDE BAR

Justification for using viral inserts ignores scientific opinion

According to a paper by Latham and Steinbrecher, [35] "The views of many scientists working in this’ area (as reflected in the scientific literature) are at odds with the policy of widespread commercialization of virus-containing GM crops being pursued by the USDA." But in spite of the concerns raised by numerous scientists that viral inserts in GM crops may recombine with other plant viruses,[36] biotech companies and regulatory agencies have ignored the data and cling to unproven or obsolete safety assumptions. Here are five commonly used arguments by advocates, with Latham and Steinbrecher’s response.

1. The likelihood of recombination is the same as that of natural plants that have two (or more) viral infections. Since that occurs naturally, we shouldn’t consider GM plants as a special cause for concern. [37]

With GM crops, viruses will come into proximity with the transgene at a much higher rate. Most natural plants are not infected by viruses and do not have viral sequences available. When viruses do attack plants, they are often restricted to certain types of tissue[38] and will not readily encounter viruses present in other tissue. For those attacking the same tissue, some viruses have a mechanism (superinfection exclusion) to prohibit other viruses from infecting the same cell.[39] In other cases, viruses may occupy different compartments within the cell and thus be prevented from interacting. These natural barriers to viral recombination are largely dismantled in GM crops, which contain viral sequences in every cell.

2. The quantities of messenger RNA (mRNA) produced by some viral inserts is less than those found in natural viruses. Therefore, the rate of recombination (of the mRNA) will be lower. [40]

Naturally occurring viruses are usually surrounded (encapsidated) by a protective coat of protein and many also replicate in areas of the cell that are enclosed by membranes.[41] GM viral sequences are neither encapsidated, nor enclosed. They therefore may come into contact with natural viruses more often, even if the total amount of mRNA is less. Furthermore, the level of transgenic mRNA may increase in those cells that are infected by a non-target virus,[42] because the introduced virus may disable the mechanism that keeps the transgene expression low.[43]

3. Argument: Recombinant viruses "are unlikely" to survive competition from pre-existing viruses or will not give rise to significant new strains.[44]

These assertions are not supported by data.[45] On the contrary, new and significant viruses do arise naturally by recombination[46](as well as mutation) and some demonstrate superior fitness compared to their parents.[47] Also, some viruses don’t compete with pre-existing ones, but rather move into a difference niche.

4. Argument: Viral sequences are inserted into GM crops so that the plants resist viruses that carry that same sequence. When the USDA approved the first virus-resistant plant (the ZW-20 squash), [48] they argued that if the inserted viral sequence recombines with a natural virus, the new virus will be suppressed by the same mechanism.

This assumption has been overturned by the more recent discovery that infecting viruses can disable the gene silencing mechanism.[49]

All four of the arguments above appear in every application for new GM virus-resistant varieties and are the primary defense against the risk of recombination. A fifth rationale, which is sometimes used by advocates, is as follows.

5. Argument: The widespread use of GM virus resistant plants will so effectively reduce the prevalence of viruses, that it will reduce the rate of recombination. [50]

No data is presented to support this position, which overstates a GM crop’s ability to suppress viruses beyond one or a few targeted strains.

Jeffrey Smith is the author of the international bestseller, Seeds of Deception. The information in this article presents some of the numerous health risks of GM foods that will be presented in his forthcoming book, Genetic Roulette: The documented health risks of genetically engineered foods, due out in the fall.
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This article used as its primary source, the following article, combined with personal communication with Dr. Jonathan Latham. Jonathan R Latham, PhD and Ricarda A Steinbrecher, PhD, Horizontal gene transfer of viral inserts from GM plants to Viruses, GM Science Review Meeting of the Royal Society of Edinburgh on "GM Gene Flow: Scale and Consequences for Agriculture and the Environment" 27 January 2003 - amended February 2004 www.econexus.info/pdf/Horizontal-Genes-virus-2004.pdf

[1] http://www.greenpeace.org/raw/content/international/press/reports/FailureGEPapayainHawaii.pdf

[2] Comments on GM Science Review, From Econexus, the Five Year Freeze, Friends of the Earth, GeneWatch UK, Greenpeace, the Soil Association, and Dr Michael Antoniou, October 14th 2003 [3] Nearly every type of virus protein has this ability: viral coat proteins (A),, viral movement proteins (B); viral replicase proteins (C); viral proteins involved in overcoming host defenses(D) and miscellaneous viral proteins(E). (A) E.g Taliansky, M. E., and Garcia-Arenal, F. (1995). Role of cucumovirus capsid protein in long-distance movement within the infected plant. J Virol 69(2), 916-22; Briddon, R. W., Pinner, M. S., Stanley, J., and Markham, P. G. (1990). Geminivirus coat protein gene replacement alters insect specificity. Virology 177(1), 85-94; (B) E.g Cooper, B., et al. (1995). A defective movement protein of TMV in transgenic plants confers resistance to multiple viruses whereas the functional analog increases susceptibility. Virology 206(1), 307-13; Ziegler-Graff, V., Guilford, P. J., and Baulcombe, D. C. (1991). Tobacco rattle virus RNA-1 29K gene product potentiates viral movement and also affects symptom induction in tobacco. Virology 182(1), 145-55; (C) Siegel, R. W., Adkins, S., and Kao, C. C. (1997). Sequence-specific recognition of a subgenomic RNA promoter by a viral RNA polymerase. Proc Natl Acad Sci U S A 94(21), 11238-43; Teycheney, P. Y., et al. (2000). Synthesis of (-)-strand RNA from the 3' untranslated region of plant viral genomes expressed in transgenic plants upon infection with related viruses. J Gen Virol 81(4), 1121-6; (D) Pruss, G., et al (1997). Plant viral synergism: the potyviral genome encodes a broad-range pathogenicity enhancer that transactivates replication of heterologous viruses. Plant Cell 9(6), 859-68; Sonoda, S., et al. (2000). The helper component-proteinase of sweet potato feathery mottle virus facilitates systemic spread of potato virus X in Ipomoea nil. Phytopathology 90, 944-950; and (E) Agranovsky, A.A. et al. (1998). Beet yellows closterovirus HSP70-like protein mediates the cell-to-cell movement of a potexvirus transport-deficient mutant and a hordeivirus-based chimeric virus. J Gen Virol 79 ( Pt 4), 889-95; Sunter, G., Sunter, J. L., and Bisaro, D. M. (2001). Plants expressing tomato golden mosaic virus AL2 or beet curly top virus L2 transgenes show enhanced susceptibility to infection by DNA and RNA viruses. Virology 285(1), 59-70.

[4] Hao et al 2003 The plant cell 15 1034-1048; Kong et al 2000 EMBO journal 19 3485-3495; Rubino et al 2000 Journal of General Virology 81 279-286; Dalmay et al 2001 EMBO Journal 20 2069-2077 [5] Helen Pearson, What is a Gene?, Nature, Vol 441, May 25, 2006 [6] Lewis, B. P., Burge, C. B. and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.

[7] Minoo Rassoulzadegan et al, RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse, Nature 441, 469-474, May 25, 2006 [8] Lolle, S. J., Victor, J. L., Young, J. M. & Pruitt. R. E. Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis, Nature 434, 505 509 (2005).

[9] Cretenet, M., Goven, J., Heinemann, J.A., Moore, B. and Rodriguez-Beltran, C. 2006. Submission on the DAR for Application A549 Food Derived from High-Lysine Corm LY038: to permit the use in food of high-lysine corn. www.inbi.canterbury.ac.nz.

[10] Cogoni, C. and G. Macino (2000). "Post-transcriptional gene silencing across kingdoms." Curr. Opin. Genet. Develop. 10: 638-643; and Timmons, L., D. L. Court, et al. (2001). "Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans." Gene 263: 103-112.

[11] Timmons, L., D. L. Court, et al. (2001). "Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans." Gene 263: 103-112.

[12] Zhao, Z., Y. Cao, et al. (2001). "Double-Stranded RNA Injection Produces Nonspecific Defects in Zebrafish." Develop. Biol. 229: 215-223.

[13] Jack Heinemann et al, Submission on Application A549 Food Derived from High Lysine Corn LY038: to permit the use in food of high lysine corn, Submitted to Food Standards Australia/New Zealand (FSANZ) by New Zealand Institute of Gene Ecology, January 22, 2005.

[14] Cretenet, M., Goven, J., Heinemann, J.A., Moore, B. and Rodriguez-Beltran, C. 2006. Submission on the DAR for Application A549 Food Derived from High-Lysine Corm LY038: to permit the use in food of high-lysine corn. www.inbi.canterbury.ac.nz.

[15] Collonier C, Berthier G, Boyer F, Duplan M-N, Fernandez S, Kebdani N, Kobilinsky A, Romanuk M, Bertheau Y. Characterization of commercial GMO inserts: a source of useful material to study genome fluidity. Poster presented at ICPMB: International Congress for Plant Molecular Biology (n°VII), Barcelona, 23-28th June 2003. Poster courtesy of Dr. Gilles-Eric Seralini, Président du Conseil Scientifique du CRII-GEN, www.crii-gen.org; also "Transgenic lines proven unstable" by Mae-Wan Ho, ISIS Report, 23 October 2003

[16 ] Andreas Rang et al, Detection of RNA variants transcribed from the transgene in Roundup Ready soybean Eur Food Res Technol (2005) 220:438 443.

[17] Joe Cummins, Transgenic virus resistant plums, June 11, 2006 [18] Jack Heinemann et al, Submission on Application A549 Food Derived from High Lysine Corn LY038: to permit the use in food of high lysine corn, Submitted to Food Standards Australia/New Zealand (FSANZ) by New Zealand Institute of Gene Ecology, January 22, 2005.

[19] Dasgupta, R., Garcia, B. H., 2nd, and Goodman, R. M. (2001). Systemic spread of an RNA insect virus in plants expressing plant viral movement protein genes. Proc Natl Acad Sci U S A 98(9), 4910-5.

[20] Jonathan R Latham, PhD and Ricarda A Steinbrecher, PhD, Horizontal gene transfer of viral inserts from GM plants to Viruses, GM Science Review Meeting of the Royal Society of Edinburgh on "GM Gene Flow: Scale and Consequences for Agriculture and the Environment" 27 January 2003 - amended February 2004 [21] Mark, Varrelmann et al, Transgenic or Plant Expression Vector-Mediated Recombination of Plum Pox Virus, JOURNAL OF VIROLOGY, Aug. 2000, p. 7462 7469 Vol. 74, No. 16 [22] Borja M, Rubio T, Scholthof HB, et al. (1999) Restoration of wild-type virus by double recombination of tombusvirus mutants with a host transgene. MPMI 12: 153-162 1999 [23] Jonathan R Latham, PhD and Ricarda A Steinbrecher, PhD, Horizontal gene transfer of viral inserts from GM plants to Viruses, GM Science Review Meeting of the Royal Society of Edinburgh on "GM Gene Flow: Scale and Consequences for Agriculture and the Environment" 27 January 2003 - amended February 2004 [24] Gibbs M (1994) Risks in using transgenic plants? Science 264: 1650-1651

[25] Weiland I and Edwards M (1996) A single nucleotide substitution in the alpha a gene confers oat pathogenicity to barley stripe mosaic virus strain ND18. MPMl9: 62-67 [26]Comments on GM Science Review, From Econexus, the Five Year Freeze, Friends of the Earth, GeneWatch UK, Greenpeace, the Soil Association, and Dr Michael Antoniou, October 14th 2003 [27] In Gibbs, et al, 1999 PNAS 99 8022-27, there is a report of a hypbrid vertebrate/plant virus that infects plants. In De Medeiros, et al., 2005 PNAS 2005 vol 102 1175-80, Also available is de medeiros et al 2005 PNAS 2005 vol 102 1175-80, a gene from an insect was expressed in human cell lines, and allowed the cells to become infected by a plant virus (tomato spotted wilt virus).

[28]Jack Heinemann et al, Submission on Application A549 Food Derived from High Lysine Corn LY038: to permit the use in food of high lysine corn, Submitted to Food Standards Australia/New Zealand (FSANZ) by New Zealand Institute of Gene Ecology, January 22, 2005.

[29] Robert Wisner, Genetically Modified Wheat is Still a Market Risk, WORC May 2005 www.worc.org/pdfs/wisnersummary-05-05.pdf

[30] Washington Post (May 11, 2004). Monsanto Pulls Plan To Commercialize Gene-Altered Wheat, http://www.washingtonpost.com/wp-dyn/articles/A15998-2004May10.html

[31] According to the Canadian Food Inspection Agency, Plant Biosafety Office, the GE flax was deregistered on April 1, 2001; The Leader Post (June 22, 2001) GM flax off the market [32]Wall Street Journal (April 27, 2001) Refiners shun bioengineered sugar beets, frustrating plans for Monsanto, Aventis, http://www.biotech-info.net/refiners_shun.html

[33] Schubert R. (Feb. 22, 2002) GE rice resistance - market rejects gene-altered crop, http://www.cropchoice.com/leadstry0137.html?recid=595

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