GENTECH archive 8.96-97


RE. question on CaMV and viruses

> (jim mcnulty)
>Subject:RE. question on CaMV and viruses
> Resent-Date: 9 Oct 1997 15:17:34 -0000
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>Date: Thu, 9 Oct 1997 16:29:23 -0400
>From: Richard Wolfson <>
>Subject: question on CaMV and viruses
>X-Mailing-List: <> archive/latest/76
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>I received the following request:
>>>Hello, I am doing research for an article on the dangers of
>>>bioengineered foods, specifically the danger of new diseases arising from
>>>the "special nature of recombination" i.e. the recombination of cauliflower
>>>viruses or the possibility of the recombination of CaMV with Hepatitis B or
>>>HIV to form even deadlier diseases of potentially epidemic proportions?
>>>That sounds very scary indeed! (eliminate the excess population in no time
>>>at all . . .) I think the public should be informed of this danger and I
>>>have an interested editor. Please dispatch as much information as possible!
>Unfortunately, I do not have the info on CaMV and viruses and genetic
>engineering, etc.  that was being distributed on the internet some weeks
>Does anyone have information on this that they could share with me and I
>could pass on?  Thank you.
>Council for Responsible Genetics
>Consumer Alert
> FDA approval of flavr savr tomato paves the road for genetically engineered
>                                   foods.
>The flavr savr tomato:
>The May 1994 FDA approval of Calgene's Flavr Savr tomato represents the
>onslaught of a new set of dangers to unsuspecting consumers. Joining
>chemical pesticides and chemical additives as potential health risks in our
>food are the products of genetic engineering. Calgene's tomato marks a major
>turning point for the industry, as its approval facilitates the accelerated
>introduction of future products.
>Marketed under the brand name "MacGregor's," this tomato is the result of
>$95 million of research and development. Calgene's technicians have isolated
>a gene that codes for an enzyme involved in the ripening process and
>reversed it to block its expression. This allows the tomato five extra days
>to ripen on the vine and still maintain firmness during shipping. Its
>extended shelf life allows for production in far away places such as Central
>America, where pesticide and labor standards are less stringent than in the
>U.S. In fact, Calgene has already contracted with Mexican growers for land
>to be used in production of the Flavr Savr.
>What is genetic engineering?
>Genetic engineering-also known as "gene splicing" and "recombinant DNA
>technology"-is a set of techniques for reconstructing the genetic
>constitution of an organism. Operating at the molecular level, this process
>involves the addition, deletion or reorganization of pieces of an organism's
>DNA (known as genes) in order to alter that organism's protein production.
>Scientists at many of the world's largest food companies are using gene
>splicing techniques to combine genes from unrelated organisms to create new
>food products.
>What is genetic engineering doing in our food?
>Uses of genetic engineering range from medical and pharmaceutical to
>industrial crops and food products. The USDA reports that for food related
>patents, 98 percent of genetic alterations are done to make food production
>and processing easier and more profitable for the companies doing it. Only
>two percent are aimed at improved taste or nutrition.
>Projects include experimenting with tomatoes by inserting "anti-freeze"
>flounder genes to resist frost. Human genes have been spliced into pigs,
>producing leaner animals. A variety of bacterial, animal, plant and viral
>genes are being spliced into crops to alter growth, create pest resistance
>and improve processing traits.
>Are genetically engineered foods safe?
>Biotechnology is a newcomer to the food industry. We have little experience
>with the unique risks posed by genetically altered foods, and no long term
>data on which to base decisions. These are some of the potential risks which
>warrant careful investigation:
>     All allergies are caused by proteins; genetic engineering involves
>     adding new proteins to altered products. The FDA warns that new
>     proteins in foods might cause allergic reactions in some people. An
>     individual allergic to peanuts, for example, might suffer distress or
>     even fatal shock from eating a tomato with a peanut gene engineered
>     into it.
>Antibiotic Resistance:
>     To determine whether new genes have been successfully incorporated into
>     an organism, scientists link the desired gene to a "marker" gene whose
>     outward expression is obvious. The most commonly used marker gene
>     confers resistance to the antibiotic kanamycin. In this case, organisms
>     which successfully undergo genetic engineering survive otherwise lethal
>     doses of the antibiotic (the Flavr Savr tomato is an example of this
>     technique). The FDA recognizes a strong possibility that consuming
>     foods which have undergone this process may lead to the development of
>     human resistance to certain antibiotics.
>     Many plants naturally produce a variety of compounds that may be toxic
>     to humans or alter food quality. Examples include neurotoxins, enzyme
>     inhibitors and hemolytic substances. Generally, these compounds are
>     present in today's food at levels that do not cause acute toxicity.
>     However, the FDA notes that such toxicants may be produced at unusually
>     high levels as a result of genetic engineering.
>Diminished Nutritional Quality:
>     A possible consequence of genetically manipulating food is an
>     alteration of the nutritional content of the resulting product. The FDA
>     cautions that nutritional value could be significantly decreased
>     without the crop exhibiting any outward signs.
>Counterfeit Freshness:
>     Humans have come to rely on certain characteristics of fruits and
>     vegetables to indicate nutritional quality and flavor. For example,
>     bright color in peppers, apples and other fruits is generally
>     associated with taste and ripeness. Genetic engineering may mislead
>     consumers into buying fruits and vegetables with the appearance of
>     ripeness, but lacking the accompanying nutritional quality or flavor.
>Unpredictable Gene Expression:
>     Genes form a holistic system, with one gene affecting multiple traits
>     and multiple genes affecting one trait. Consequently, scientists cannot
>     always predict how a single gene will be expressed in a new system. For
>     example, splicing a gene for human growth hormone into mice produces
>     very large mice; splicing the same gene into pigs produces skinny,
>     cross-eyed, arthritic animals. The FDA warns that splicing a single
>     gene into an organism for a single desired effect may unintentionally
>     cause other harmful reactions within that organism which are not
>     detectable.
>Environmental Concerns:
>     Organisms engineered to grow under adverse conditions run the risk of
>     either becoming or creating (by breeding with wild relatives) new
>     strains of weeds. Such organisms could grow out of control in areas not
>     intended for them, causing millions of dollars in damage to
>     agricultural lands and immeasurable destruction to sensitive
>     ecosystems. A second major environmental concern is the increased use
>     of herbicides. Over half of the crops currently under development are
>     those engineered for herbicide resistance, permitting increased use of
>     these harmful chemicals.
>Religious And Ethical Issues:
>     Genetic engineering creates legitimate religious and ethical dilemmas
>     for many consumers. Individuals wishing to avoid certain foods (i.e.,
>     for vegetarian or religious reasons) may prefer not to eat vegetables
>     with animal genes engineered into them. Many people may not wish to
>     consume foods containing human genes. Without proper labeling it will
>     be impossible for consumers to exercise their right to choose what kind
>     of foods they eat.
>What is the FDA Policy for Regulation of Genetically Engineered Foods?
>     The FDA has shrugged its responsibility for regulating genetically
>     engineered foods. Even though the agency recognizes most of the above
>     dangers as potential hazards, under its current policy most
>     bioengineered products will be regulated as if they were unprocessed
>     foods with no additives. In most cases, products will not require a
>     pre-market approval process, public notification, or any labeling
>     whatsoever to inform consumers of their novel and possibly harmful
>     characteristics; a precautionary "safety proven first" policy has been
>     scrapped in favor of corporate economic interests.
>Industry will essentially be on an "honor system," deciding when and whether
>to consult with the FDA. Companies conduct safety tests for their own
>bioengineered products, notifying the FDA only if they suspect a problem. If
>they perceive no danger to consumers, companies are not required to state
>that their product has been genetically manipulated or to reveal the source
>of implanted genes; nor are they required to make the results of their
>safety tests available to the public. The FDA will not have a complete set
>of information regarding genetically engineered foods on the market, so
>there will be no way to trace who or what is responsible should a problem
>occur. Not only does the FDA policy forfeit consumers' right to know how
>their food has been manufactured, it also impedes the public's right to safe
>and tested food products by allowing the companies that profit from
>biotechnology to decide if and when a product is hazardous.
>The basis of this policy is the inaccurate premise that genetic engineering
>is only a minor extension of traditional breeding, not significant enough to
>warrant a unique policy for this technology. Genetic engineering operates by
>transferring specific genes directly into the product-organism itself,
>eliminating the role of parents and reproduction. This new method allows for
>the addition or deletion of proteins in ways not possible through
>reproduction, creating organisms missing essential proteins or harboring
>entirely new ones. The FDA chose to treat transferred genes as natural food
>products as long as they come from an approved food source, thereby failing
>to consider the unpredictable effects which the old gene may have in its new
>Why did the FDA leave the wolf guarding the hen house?
>Genetic technology can drastically transform the food production industry.
>Agricultural products may be engineered to be produced in factories;
>tropical products may be engineered to be grown in industrialized nations
>with temperate climates; new products can be created to out-compete and
>out-produce all existing crops; small farmers will become reliant on the
>patented seeds of the biotech industry.
>The FDA policy exists as an outdated leftover from the Reagan!Bush
>administration's neglect of health and safety standards in favor of industry
>profits. The Clinton administration, elected with consumer and
>environmentalist support, is wrongfully allowing this misguided and
>dangerous policy to continue. The time has come for the FDA to reevaluate
>its position on genetically engineered foods, and for citizens to demand a
>consumer!centered regulatory policy.
>What Would be a Safer and More Responsible Policy?
>     Under the food additive law, the burden of demonstrating safety should
>     be on those who add new substances to foods. If genetic engineering was
>     treated as the novel process it is, regulation would demand the
>     rigorous and independently!verified proof of safety expected of
>     chemical additives. Given the lack of evidence to support claims that
>     genetically engineered foods are safe, increased testing is essential
>     to maintain both the safety of the food supply and public trust.
>     The FDA must require industry to notify them when any genetically
>     engineered food goes on the market. In the event of problems, this
>     would provide a "trail" for scientists and regulators to follow to
>     determine the origins of an unsafe product.
>     Mandatory labeling of all genetically engineered food products is the
>     minimum requirement necessary to ensure product safety. This will
>     protect a consumer's right to choose whether or not to purchase these
>     products.
>Social Utility:
>     In the European Community, along with the three criteria of safety,
>     efficacy and quality, genetically engineered foods must also
>     demonstrate that they present no adverse socio-economic impacts. An
>     ideal FDA policy would mandate that the biotech industry be required to
>     demonstrate the social utility of any proposed food modification.
>What Can We Do?
>[A small amount of adjustment can be made for national differences - the
>principles are the same anywhere]
>  1. Write to the FDA: If you are concerned that the Food and Drug
>     Administration's policy will not adequately safeguard our food supply
>     and does not respect our right to know what is in the food we eat, then
>     write to (or call) the FDA commissioner immediately:
>     Dr. David Kessler
>     FDA Commissioner
>     HF - 1
>     5600 Fishers Lane
>     Rockville, MD 20857
>     (301) 443-2410
>     Let the FDA know that you want federal policy on genetically engineered
>     foods to set a higher standard of safety and require:
>        o extensive pre-market testing of genetically engineered foods as
>          "food additives" to ensure the safety of these new products before
>          they are introduced into the food supply;
>        o o pre-market notification to the FDA of a company's intent to
>          introduce a new product at least 90 days in advance to facilitate
>          tracking should problems occur;
>        o o mandatory labeling of all genetically engineered foods approved
>          for market, so that citizens can make fully informed choices about
>          the food we eat.
>  2. Contact local grocery stores, restaurants & school cafeterias:
>     Encourage local food distributors to boycott genetically engineered
>     products. Ask them to write to the FDA to demand labeling of
>     genetically engineered foods, so that consumers will know what kind of
>     products they are buying.
>  3. Share your concerns with your congressional representatives
>  4. Support the work of the CRG: The CRG is fighting to protect your right
>     to make informed consumer choices. For $35 you can become a CRG
>     Associate and receive our newsletter, GeneWATCH, action alerts, and
>     additional updates. Or, you can subscribe to GeneWATCH for just $24 a
>     year. Larger contributions are welcome and appreciated, and are
>     tax-deductible. As we accept no government funds, we depend upon a
>     growing number of individuals for financial support.
>                     The Use of Cauliflower Mosaic Virus
>      35S Promoter (CaMV) in Calgene's Flavr Savr Tomato Creates Hazard
>Joseph E. Cummins
>Associate Professor (Genetics)
>Dept. of Plant Sciences
>University of Western Ontario
>London, Ontario
>N6A 5B7
>Telephone: (519) 679-2111 Ext. 6478
>Answering Machine: (519) 681-5477
>FAX: (519) 661-3935
>June 3, 1994
>"Feel free to reprint this article in unalterated form"
>The majority of crop plant constructions for herbicide or disease resistance
>employ a Promoter from cauliflower mosaic virus (CaMV). Regardless of the
>gene transferred, all transfers require a promoter, which is like a motor
>driving production of the genes' message. Without a promoter, the gene is
>inactive, but replicated, CaMV is used because it is a powerful motor which
>drives replication of the retrovirus and is active in both angiosperms and
>gymnosperms. The CaMV pararetrovirus replication cycle involves production
>vegetative virus containing RNA which is reverse transcribed to make DNA
>similar to HIV, Human Leukemia Virus and Human hepatitis B. (Bonneville et
>al. RNA Genetics Vo.11, Retroviruses, Viroids and RNA Recombination pp.
>23-42, 1988). CaMV is closely related to hepatitis B and is closely related
>to HIV (Doolittle et al. Quart.Rev.Biol. 64,2, 1989; Xiong and Eickbush,
>EMBO Joumal 9, 3353, 1990). The CaMV promoter is preferred above other
>potential promoters because it is a more powerful promoter than others and
>is not greatly influenced by environmental conditions or tissue types. CaMV
>has two Promoters 19S and 35S, of these two the 35S promoter is most
>frequently used in biotechnology because it is most powerful. The 35S
>promoter is a DNA (or RNA) sequence about 400 base pairs in length. The use
>of the CaMV promoter in plants is analogous to the use of retrovirus LTR
>promoters in retrovirus vectors used in human gene therapy. The majority of
>human gene therapy trials employ LTR promoters to provide motors to activate
>Antisense genes are genes constructed to have a complementary sequence to a
>target gene, thus producing a product that combines with a gene message to
>inactivate it. Antisense is analogous to an antibody which combines with an
>antigen like a key fitting a lock. Antisense is being used to treat human
>cancer and HIV infection. Antisense is used to prevent spoilage in tomatos,
>either by targeting an enzyme degrading cell walls (polygalacturonase), or
>production of ethylene a hormone promoting ripening (P. Oeller et al.
>Genetic Engineering 49, 1989; R. Fray and D. Grierson, Trends Genetics 9,
>438, 1993). Most frequently antisense targets production of a chemical
>metabolite producing ethylene. The antisense gene also influenced polyamines
>spermine and spermidine production through S-adenosylmethionine. The
>implication is that the plant antisense gene product should be tested in
>animals to ensure that critical functions including gene replication, sperm
>activity and gene imprinting are not disrupted.
>The perceived hazards of CaMV in crop plants include the consequences of
>recombination and pseudo recombination. Recombination is the exchanges of
>parts of genes or blocks of genes between chromosomes. Pseudorecombination
>is a situation in which gene components of one virus are exchanged with the
>protein coats of another. Frequently viruses may incorporate cellular genes
>by recombination or pseudorecombination, it has been noted that such
>recombinants have selective advantages (Lai, Micro. Rev. 56, 61, 1992).
>It has been shown that the CaMV genes incorporated into the plant (canola)
>chromosome recombine with infecting virus to produce more virulent new virus
>diseases. The designers of the experiment questioned the safety of
>transgenic plants containing viral genes (S. Gal et al., Virology 187: 525,
>1992). Recombination between CaMV viruses involves the promoter (Vaden and
>Melcher, Virology 177: 717, 1992) and may take place either between DNA and
>DNA or RNA and RNA and frequently creates more severe Infections than either
>parent (Mol. Plant-Microbe Interactions 5, 48, 1992). Recently related
>experiments suggest altered plants may breed deadlier diseases (A. Green and
>R. Allison, Sciences 263: 1423, 1994). DNA copies of RNA Viruses are
>frequently propagated using the CaMV 35S promoter to drive RNA virus
>production (J.Boyer and A. Haenni, Virology 198: 4l5, 1994 and J.Desuns and
>G.Lomonossoff, J. Gen. Vir. 74: 889, 1993). In conclusion CaMV promoters
>recombine with the infecting viruses to produce virulent new diseases. CaMV
>viruses and promoter may incorporate genes from the host creating virulent
>new diseases.
>CaMV can recombine with insect viruses and propagated in insect cells (D.
>Zuidema et al. J. Gen. Vir. 71: 312, 1990). Thus it is likely that as large
>numbers of humans consume CaMV modified tomatos recombination between CaMV
>and hepatitis B viruses will take place creating a supervirus propagated in
>plants, insects and humans.
>Plant biotechnology has grown out of recombinant DNA research that began in
>the early 1970's. The special nature of recombination has been debated since
>that time. In recent years, government regulators on the American and
>European continents, under pressure from well-funded lobby representing the
>biotechnology industry, have chosen to ignore the special nature of
>recombination. They have chosen instead to base regulations on existing
>frameworks for toxic chemicals and pathogenic organisms. Ignoring the
>special nature of recombination is likely to have costly, if not terminal,
>environmental consequences. A worst-case example includes the complete
>cloning of Human Immunodeficiency Virus (HIV) on an E. coli plasmid. When
>the plasmid is used to transform animal cells, intact HIV viruses are
>released from the cells. A careless (but legal) release of HIV bacteria to
>the environment would allow the plasmid to transfer to Salmonella as well as
>E. coli. Thus, numerous mammals and birds could contain HIV bacteria which
>could transform the animals, which would in turn produce HIV particles
>unable to target the animals T-cell receptors but easily transmitted to
>humans. When all the animals are HIV carriers, human survival would be
>marginal. The special concerns of recombination in plant biotechnology
>include the viruses and bacteria used in crop plant construction and gene
>flow between related crop plants and weeds in the field.
>Currently most experts agree that virus diseases such as influenza gain
>strength for epidemics by alternating between animal hosts (pigs and ducks)
>and man. Epidemics begin when rare combinations appear in large closely
>associated populations such as in asia. CaMV can propagate in plant and
>insect hosts following recombination. It may not be outlandish to predict
>that CaMV may recombine with related Hepatitis B or for that matter HIV to
>create a most powerful disease. The salient feature being large number of
>people or animals consuming large numbers of virus genes incorporated into
>crop plants making up a major part of human and animal diet.
>The use of CaMV promoter is seldom an issue in reviews of safety of gene
>tinkered crops. Few people have raised the important issue and more often
>than not their concerns are ignored by government officials "protecting"
>public safety. This omission may be a fatal one because it has potentially
>the most damaging impact, and the one perceived at the beginning of gene
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