Cauliflower Mosaic Virus (CaMV)

The most common virus DNA used in genetic engineering is the promoter of the Cauliflower Mosaic Virus (CaMV) used in plant genetic engineering. It is used in almost every case, including the presently most culitvated GE crops, the RoundupReady (RR) Soy of Monsanto, the Bt-Maize of Novartis, GE cotton and various varieties of GE Canola, a rapeseed variety widely cultivated today especially in Canada. Experiments have shown that the CaMV promoter may recombine with infecting genes yielding new viruses that may be more infectious than the natural viruses. For more details, see also "The Cauliflower Mosaic Virus promoter - a hazard in GE plants")

Recent research confirms these findings and indicates that the risks for combination with unrelated viruses is even greater than formerly understood. Studies have demonstrated that CAMV has a so called "recombination hotspot" which makes it prone to break up other DNA chains and join them at that point.

Mae-Wan Ho, biologist, Angela Ryan molecular biologist and Joseph Cummins, geneticist, have recently published a paper warning for the use of CaMV in crops.

This virus gene, they write, has the potential to reactivate dormant viruses or create new viruses in all species to which it is transferred. The development of cancer is another potential consequence.

The scientists "strongly recommend that all transgenic crops containing CaMV 35S or similar promoters should be immediately withdrawn from commercial production or open field trials. All products derived from such crops containing transgenic DNA should also be immediately withdrawn from sale and from use for human consumption or animal feed". Full text press release here. [ML] Full text here. [AL]

Also the US Department of Agriculture has expressed concern about such high-risk sequences that may trigger the process of viral replication":

Concerns at USDA about viral high-risk sequences

"..... At a meeting in Washington DC last week [Aug 1997], the US Department of Agriculture outlined possible restrictions aimed at reducing the risk of creating harmful new plant viruses .....These include a possible limit on the length of genetic sequences introduced into crop plants and the banning of genes that make functional proteins. The department is also worried about particularly high-risk sequences, such as those that trigger the process of viral replication."

[The CaMV DNA in GE crops is such a high risk sequence. It is still widely used in GE crops covering a large part of American fields. /The editor.]

[The suggested restrictions have not since been implemented to the best of our knowledge. /The editor]

Source: New Scientist magazine, 16 August 1997: "Field of genes: They have the biotechnology, but it may be running out of control, and the US is starting to worry"

Virus genes used for increasing disease resistance

Another possibly dangerous practice is the use of virus parts to make plants resistant to infecting viruses. Certain virus genes, coding for the virus protein capsule , are used for this purpose. These so called "capside genes" are combined with the CaMV promoter to ensure that they will be active in the host. Also the capsied genes have a propensity to recombine with invading viruses to create new pathogens that tend to be more aggressive than the original virus.

New viral pathogens could have an enormous impact on economically important crops, requiring considerable control costs. Source: Rissler, J. and M. Mellon. 1996. The Ecological Risks of Engineered Crops. Cambridge, MA: MIT Press.

Sattelite RNA's

Another method to achieve increased virus resistance has been to insert so called viral "satellite RNA's". These genes are known to reduce the damage from a virus infection. But recent research found that such genes, when inserted into cucumbers, very often mutated into harmful variants (ref. Paulikaits P. And Rossinck MJ (1996). "Spontaneus change of a benign satellite RNA of cucumber mosaic virus to a pathogenic variant. Nature Biotechnology 14: 1264-1268).

Epidemics of new viruses might appear

Dr Joe Cummins, Professor Emeritus of Genetics at University of Western Ontario, Canada fears that the insertion of viruses may give rise to new plant disorders that may wipe out whole harvests. One plant only contains hundreds of millions of cells, each containing a CaMV virus gene. Anyone of these genes may combine with an infecting virus, generating a new virus.

It is not possible to estimate the size of the risk for the appearance of new virus diseases from genetically engineered virus parts in crops beacuse there is not enough research data available. Some researchers believe the risk is very small and others believe it is large enough to justify a prohibition of the use of virus parts in genetic engineering. But in the absence of sufficient research data, this is nothing but guesses. Considering the experimental evidence we can only say today that there is definitely a risk but of unknown size.

The serious thing is that it has been repeatedly shown experimentally that the new viruses may be more contagious and damaging and may also cross species borders. So viruses specialized on just one plant species might become infectious to other species. It is enough that one very malignant virus appears in only one cell for a new dangerous virus epidemic to appear.

Risk for harmful "GE viruses" spreading in USA and Canada?

About 30 percent (27 million acres) of the crop in USA of 1998 is calculated to be RR Soy. Also a large crop of GE Maize has been planted (19,6 million acres). In Canada, large crops of Canola are cultivated (about 7 million acres). Every cell in the present GE crops in USA and Canada contains virus genes. One plant only contains hundreds of millions of cells. The number of plants in the GE crops in North America is altogether thousands of billions.

Even if the scientists would be right who guess that the statistical risk is very small, the appearance of new hazardous viruses might be more likely than they may have realized. This is because they may have forgotten to consider the enormous large numbers of possible recombination events in one annual crop in USA + Canada. A corn plant, for example, contains about 1 billion cells and there is one CaMV promoter in each cell. There are about 50.000 plants in an average field, which means 50.000 billion recombination prone promoters per field. The gigantic acreage of of US GE crops therefore can be seen as a huge "experimental ground" for generation of new viruses with unpredictable and potentially hazardous outcomes. Even if the probability of a new dangerous virus to be generated would be extremely small, such an event may still occur due to the very large number of recombination opportunities present. Here is an analogy for you who are not so used to thinking in these terms:

Suppose there is a lottery with a million tickets. Then the chance of winning with one ticket is one on a million. But if you buy all the tickets, your chance will transform to 100% probability of winning. Every cell in the huge GE crop in North America is a "ticket" in the virus lottery. And there are zillions of cell "tickets" in the crop. Therefore, even if the chance for "winning" - for a new virus to turn up - would be extremely small, it may be likely to occur. Scientific laboratory experiments indicate that this probability may not be very small.

Even a single new very contagious virus strain might cause important damage, as it would rapidly multiply and might spread to a significant part of the crop. As it has been shown that GE-genes can readily be transferred to related weeds, these will become an uncontrollable reservoir of such virus genes even when cultivation of GE crops would cease. A highly contagious virus with low species specificity could in the worst case cause extensive damage to the crops and the ecology.

Conclusion

It has been scientifically established that new viruses may result from recombination with virus parts existing in GE organisms. Some studies indicate that these new viruses may become more harmful and less species specific that "natural" viruses. The size of this risk is unknown. Even if the statistical risk for the emergence of dangerous new viruses would be very small, they may still appear in North America as the number of GE virus genes in the crops is now extremely large.

One single new and highly contagious virus generated in this way might spread to a signficant part of the crops and cause extensive damage. There is presently no scientific basis for denying this possibility or even for saying that it is very unlikely as the size of the risk has not been investigated.

This is one of the reasons why we find it necessary to have a moratorium on the release of genetically engineered organisms. In addition, all presently cultivated GE crops should be withdrawn from the market.

Related articles

GM Expert Warns Of Cancer Risk From Crops

By Rob Edwards, Environment editor
Sunday Herald
December 08, 2002

Demand for Executive to ban crop trials until effects of GM food on health are studied

Eating genetically modified (GM) food could give you cancer. That is the stark warning today from one of Scotland's leading experts in tissue diseases.

Dr Stanley Ewen, a consultant histopathologist at Aberdeen Royal Infirmary, says that a cauliflower virus used in GM foods could increase the risk of stomach and colon cancers.

He is calling for the health of people who live near the farm-scale GM crop trials in Aberdeenshire, Ross-shire and Fife to be monitored. Their food and water will be contaminated by GM material, he said, which could hasten the growth of malignant tumours.

'I don't want to be scare-mongering, I want to be understated,' Ewen told the Sunday Herald. 'But I'm very concerned that people who rely on local produce might be endangering themselves.'

The government, backed by its scientific advisors, has always insisted the GM trials pose no risk to human health or the environment. Never theless, the trials have provoked widespread opposition, with dozens of protesters arrested for damaging GM crops.

Ewen's warning, which has been delivered to the Scottish Parliament's Health and Community Care Committee, is bound to be seized on by critics . The committee is just completing an investigation into the safety of GM food and is hoping to report its findings this week.

Ewen, who has 29 years' experience as a histopathologist, is currently leading a pilot project in Grampian to screen people for colon cancer. In 1999, along with Dr Arpad Pusztai, a former researcher at Aberdeen's Rowett Institute, he published a study suggesting that GM potatoes harm rats.

In his submission to the health committee, Ewen expressed 'great concern' about the use of the cauliflower mosaic virus as a 'promoter' in GM foods. The virus is used like a tiny engine to drive implanted genes to express themselves.

But Ewen pointed out that the virus is infectious, and could act as a 'growth factor' in the stomach or colon, encouraging the growth of polyps. The faster and bigger polyps grow, the more likely they are to be malignant, he added.

There are also risks in feeding GM products like maize to cattle, he cautioned.

'It is possible cows' milk will contain GM derivatives that can be directly ingested by humans as milk or cheese. Even a lightly cooked, thick fillet steak could contain active GM material.'

GM material can be destroyed by cooking or boiling for 10 minutes, and it can be broken down by the acids and enzymes in the stomach. But Ewen is worried that genes in uncooked GM fruit and vegetables could survive common stomach infections.

'It is possible GM DNA could affect stomach and colonic lining by causing a growth factor effect with the unproven possibility of hastening cancer formation in those organs,' he stated.

Ewen stressed that he is not opposed to all GM technology, which he believes could have real benefits, particularly in medicine. But he is sufficiently alarmed by the current use of the technology to urge the health committee to call for a ban on GM crop trials while their safety is tested on animals.

Doctors from the British Medical Association have also suggested a GM ban to the committee because of the unknown effects on health. The committee's investigation was prompted by a petition of 6000 signatures gathered by protesters who maintained a vigil at a GM trial site at Munlochy in Ross-shire.

'What is most worrying about Dr Ewen's evidence is that while his concerns are disease-specific, the risks extend to a wide range of GM food crops,' said Jo Hunt, director of the lobby group Highlands and Islands GM Concern.

'The effects are caused not by just one 'bad' DNA fragment, but are a result of the reaction of plant cells to genetic engineering itself. All the major GM food plants currently produced could have the same effect when eaten.'

Hunt argued that long-term research was needed to establish whether GM food was safe. 'But instead of looking at the impact of GM food on people's health, the Scottish Executive has spent over £5 million on farm-scale trials to see how growing GM crops on Scottish farms will affect butterflies and weeds. The Executive has already released GM at 11 sites and is considering allowing GM to be released anywhere in the country from 2004, before it knows whether GM food is safe to eat.'

The Executive also came under fire from the Scottish National Party's shadow environment minister, Bruce Crawford, who demanded a freeze on GM crops trials. 'We cannot allow GM material to enter the food chain until there are absolute guarantees that there are no risks,' he said.

He pointed out that, in a recent letter, the environment minister, Ross Finnie, had admitted to him that plants around GM crops could become contaminated . Finnie added, however, that the government's advice was 'unanimous in its conclusion that GM crops that have approval do not pose a safety threat.'

Ewen's evidence to the health committee is backed up by a separate submission from Arpad Pusztai, who now works as an independent consultant. He warned that GM contamination could jeopardise human health and cause irreversible environmental damage.

'We need to rethink the whole strategy of genetic engineering,' Pusztai said. 'Because of its potential importance for, and effect on, mankind, it should not be left to the decision of a few multinational companies.'

http://www.sundayherald.com/29821

Soul and Conscience Witness Statement
Royal Commission NZ

by Stanley William Barclay Ewen M.B.Ch.B., Ph.D., F.R.C.Path.,
Department of Pathology,
University of Aberdeen, Foresterhill, Aberdeen. AB25 2ZD

Human health

Human health issues are difficult to quantify but will usually relate to the 6th decade upwards in a "Western - type" society. Food related changes may thus be extremely difficult to detect as degenerative changes become dominant and life style indiscretions, occurring 20 years previously, easily forgotten or overlooked. BSE may have little to do with human GMO ingestion but lessons can be learned from the catastrophe that has all but destroyed British farming.

The possibility of transmission of an apparent species specific pathogen to cattle or humans was completely ridiculed initially and television pictures of a government minister feeding his baby daughter a pie potentially containing tainted meat was dramatic although reprehensible. BSE is, as the name indicates, a spongiform condition of the brain that was rare in humans and always recognised in the elderly. It was only after neurologists and neuropathologists recognised that some young people developed a clinical syndrome closely analogous to Creuzfeld Jacob disease that a new disease was perceived (NVCJD). The unwillingness of government agencies to recognise the remote possibility of a new food related disease in young adults was incomprehensible. The lesson revealed by this disaster seems clear; a new disease will only be recognised when it has unusual pathology, occurs in an unusual age group and has overt recognisable clinical features. The demonstrated proclivity for food related disease to affect the young should not be understated. Several diseases seem to affect growing children rather than fully developed adults with static body parameters. It must also be stated that no current test considered to be sufficient evidence of safety would or could have detected NVCJD. It follows that all new foods, in particular GM food, must be tested in animals, especially young animals, as the human guinea pig approach seems to be global anathema.

With these factors in mind, the present oft reiterated banal statement by regulatory authorities that many billions have eaten GM food with no reported ill effect seems misleading. As I commented at the recent WHO/FAO expert consultation in Geneva, diseases with a biological history measured in decades, such as cancer, would not be observed to be significantly increasing in the elderly or occurring in the young until several years of careful analysis of records had been compared. The specific reason for highlighting cancer is based on my meticulous measurement of changes within the gut lining in young rats fed GM potatoes for 10 days (Lancet 354, 1353-1354 16th October 1999). Despite all manner of attack, the peer reviewed published histological observations are unassailable and reveal a clear growth factor effect visualised as microscopic lengthening of the proliferative compartment of the lining of stomach and intestines. This effect may not be permanently harmful and is probably reversible after a few days of GM withdrawal but increased chronic inflammatory cells were also evident consistent with involvement of the immune system. Proliferative effects have been previously recorded following GM food ingestion viz. proliferation of stomach lining following 'Flavr Savr' tomatoes and proliferation of small intestinal lining following ingestion of transgenic potatoes by mice (Nat. Toxins (1998) 6,219-233).

Unfortunately food scientists seem oblivious of the fact that the population is not all adult and that approximately half of all adults have disease of either stomach or large intestine. The stomach disease I refer to is H.pylori infection that has been shown to be closely associated with gastric cancer. H.pylori is a micro organism that causes chronic inflammation accompanied by proliferation of the lining of the stomach and is present in 40% of the population by age 40 years. It is reasonable to suggest that additional dietary growth factors in GM food could further increase proliferative effect hastening the development of gastric carcinoma; similarly polyps in the colon could be accelerated to become invasive cancer. After several years of chronic inflammation, the stomach will change its lining to resemble the small intestine and, later still, lose the ability to produce acid and enzymes if the infection is not eradicated by powerful triple antibiotic therapy.

Ewen and Pusztai's histological results clearly indicate that the growth factor effect is not caused by the newly expressed transgenic protein but appears to be due to the gene construct inserted into the recipient DNA. The construct includes, not only the transgene, but also marker genes and a powerful promoter. Endogenous plant promoters seem unable to cause transgene expression and most success can be expected by using a viral promoter to drive foreign gene expression for example, (-carotene was not expressed in rice using endogenous promoters and a viral promoter was required to produce "golden rice". The use of a viral promoter, the infectious part of the virus, seems to be alien to food safety as the usual viral promoter is almost identical to human hepatitis B virus. Hepatitis B is endemic in African and Far Eastern populations and any possibility of intact promoter reaching liver might have unexpected effects. The possibility of gene transfer, either to resident gut commensal micro organisms or gut lining cells, is considered all but impossible. Most molecular biologists do not accept the possibility and assess the chance at 1 in 1027 although many experts suggest that 1 in 1015-18 is the reality. On the other hand, the infectious part of a virus might not be degraded in the stomach and could gain access to gut bacteria or lining cells similar to sporadic viral infection of the stomach or intestines.

The essential problem hinges on complete degradation of food proteins during digestion. Current testing of completeness of digestion relies on recombinant proteins exposed to stomach enzymes (non human source) and acid in vitro. This artificial system demonstrates that simple recombinant proteins are indeed destroyed but I do not consider this approach to be representative. Recently, a sample sent to the Pathology Department, University of Aberdeen was submitted as a possible gall stone found at the end of the small intestine during an operation. Histology revealed that the object was recognisable as a seed despite having been exposed to gastric juices , pancreatic enzymes and small intestinal enzymes during transit. The undigested seed contained identifiable DNA (confirmed by specific tests) that could have leaked from the seed during passage along the small intestine. Thus the plant cell walls prevented digestion in the upper gastrointestinal tract and horizontal gene transfer was a possibility throughout stomach and small intestine at least. Our histological experiments, referred to above, do reveal that cooking reduces the growth factor effect of GM potatoes consistent with the observation that 950C or higher, is required to degrade DNA beyond the point of genetic information transmission (Chiter et al). It could be argued that the presently available heavily processed GM products may not be capable of genetic information transmission and oil from rape seed contains almost no GM DNA. I believe that the real problem that we face is with fruits and vegetables that are usually eaten raw (the normal diet contains about 30% raw plant produce whereas the vegetarian diet will be at least twice this amount). GM fruits and vegetables have not been released as yet but have certainly been successfully produced.

Unfortunately human food is not suitable for testing in a standard toxicological experiment. In a classical toxicological investigation a single substance of defined chemical composition can be administered in identical dose to a group of laboratory animals. Even a single foodstuff is considered to be too complex to dissect out a single undesirable effect that can be acceptable as unsafe. For this reason, GM food safety relies on simple identity, by chemical analysis (substantial equivalence), compared to the parent - nutritional and metabolic effects are not considered. Unfortunately, substantial equivalence is imprecise and the degree of acceptable variation has never been stated. Undoubtedly, adequate nutritional and metabolic GM evaluation would require laboratory animal testing that would greatly increase the approval costs of GM products.

Postscript

At the time of writing (19.10.00) the local press contains a report from Prof. R. Orskov (formerly of Rowett Research Institute) who states that he will not drink milk from cows fed with GM maize until further testing is performed.

Impressions of operation of Joint FAO/WHO Expert Consultation on foods derived from Biotechnology. I was asked to submit my curriculum vitae to WHO by Consumers International and, to my surprise, I was invited to attend the above consultation meeting in Geneva on May 29 this year. I was completely unfamiliar with proceedings but most of the others present were "old hands" and immediately subverted the meeting by proposing and seconding the chairman (Kuiper). Then Mariansky was proposed and seconded as reporter and, despite protestation, was accepted as the American influence was dominant. The WHO staff seemed powerless to prevent this take over despite trying to infuse transparency by inviting others, such as myself, new to the meeting. My enduring impression was that North American, English, Dutch and Scandinavian interests were well represented although other European, Asian, South American and African interests were not. The experts, apart from one nutritionist, one epidemiologist, one economist and one pathologist, were food scientists usually from national regulatory bodies. With amazing alacrity, they stamped their dominance on the meeting and comments from the minority groups were given rather short shrift and were not incorporated into the final version of the report. The meeting was unrepresentative and financial, industrial and government interests were not fully disclosed. Food safety was in the hands of plant molecular biologists with unknown allegiance and medical aspects were simply a nuisance that impeded dominance of big industrial companies.

One subject that did receive attention - Allergenicity of GM Foods - will be the main topic for discussion at the next meeting (Rome January 2001). Allergenicity is of concern because there is no animal model available and all testing has to be done in human volunteers, preferably allergic human subjects. Several GM foods express a bacterial toxin or lectin and these proteins are resistant to cooking and digestion and will bind to, and enter, the lining cells of the intestines (usually considered a prerequisite to allergenicity). The proposal, presented at the Geneva meeting, is to use post market surveillance to detect GM food allergy despite the fact that, for some, the allergy will be fatal.

Environmental matters

There can be little doubt that reduction of biodiversity is deprecable and once GM seeds are broadcast the ensuing contamination is permanent. Thus, should any adverse effect be traced to GM plants at some point in the future then eradication will be well nigh impossible. The difficulty is that many companies have persuaded the authorities to believe that genetic engineering resembles traditional plant breeding methods. This viewpoint negates the fact that foreign DNA has been inserted into the recipient plant in a way that is completely at odds with natural breeding. Once the foreign gene has been successfully inserted a powerful promoter, usually viral, is required and most people would prefer not to eat living virus. It is possible that the promoter may not be broken down in the mammalian gut and thus the environmental contamination would include all sea life. It does appear foolhardy to promote planetary pollution unless some other motive, such as patenting with exclusive rights and substantial profits, is at stake. Unfortunately many of those on government advisory committees have clandestine financial interests and thus plant molecular biologists determine policy best suited to profit rather than complete safety evaluation. The old refrain that GM technology is required to feed the burgeoning world population is promotion by guilt. The United Nations Food and Agriculture Organisation (FAO) recently concluded that the world could be fed without GM food (Agriculture: Towards 2015-30, FAO April 2000). In Europe, current non GM agriculture is so productive that 10% of cereal land has to be kept out of production and it appears that civil strife and corrupt government is responsible for malnourishment in the Third World. Deliberate environmental pollution, in the form of US food aid sent to cyclone victims in Orissa, India, occurred last October and consisted of GM soy beans and maize rejected by traditional markets in Europe and Japan. It is claimed that the US government used the opportunity to create a market entry for GM products. This type of approach pays little heed to traditional agriculture and will severely limit future biodiversity.

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