* A MUST READ *: The Global Spread of GMO Crops - Destroying the environment, the world, food production and our health.

[Guest guest]

Genetically Modified Organisms

http://www.seedsofdeception.com/

 

 

 

 

 

DANGER - The Global Spread of GMO CropsDestroying the environment, the world, food production and our health.

 

* THIS IS A MUST READ *

By PETER MONTAGUE

January 8, 2006Felix Ballarin spent 15 years of his life developing a special organically-grown variety of red corn. It would bring a high price on the market because local chicken farmers said the red color lent a rosy hue to the meat and eggs from their corn-fed chickens. But when the corn emerged from the ground last year, yellow kernels were mixed with the red. Government officials later confirmed with DNA tests that Mr. Ballarin's crop had become contaminated with a genetically modified (GMO) strain of corn.Because Mr. Ballarin's crop was genetically contaminated, it no longer qualified as "organically grown," so it no longer brought a premium price. Mr. Ballarin's 15-year investment was destroyed overnight by what is now commonly known as "genetic contamination." This is a new phenomenon, less then 10 years old -- but destined to be a permanent part of the brave new world that is being cobbled together as we speak by a handful of corporations whose goal is global domination of food.Mr. Ballarin lives in Spain, but the story is the same all over the world: genetically modified crops are invading fields close by (and some that are not so close by), contaminating both the organic food industry and the "conventional" (non-GMO and non-organic) food industry.As a result of genetically contamination of non-GMO crops in Europe, the U.S., Mexico, Australia and South America, the biotech food industry had an upbeat year in 2005 and things are definitely looking good for the future. As genetically modified pollen from their crops blows around, contaminating nearby fields, objections to genetically modified crops diminish because non-GMO alternatives become harder and harder to find. A few more years of this and there may not be many (if any) truly non-GMO crops left anywhere. At that point there won't be any debate about whether to allow GMO-crops to be grown here or there -- no one will have any choice. All the crops in the world will be genetically modified (except perhaps for a few grown in greenhouses on a tiny scale). At that point, GMO will have contaminated essentially the entire planet, and the companies that own the patents on the GMO seeds will be sitting in the catbird seat.It is now widely acknowledged that GMO crops are a "leaky technology" -- that it to say, genetically modified pollen is spread naturally on the wind, by insects, and by humans. No one except perhaps some officials of the U.S. Department of Agriculture were actually surprised to learn this. GMO proponents have insisted for a decade that genetic contamination could never happen (wink, wink) and U.S. Department of Agriculture officials want along with the gag. And so of course GMO crops are now spreading everywhere by natural means, just as you would expect.It couldn't have turned out better for the GMO crop companies if they had planned it this way.Growers of organically-grown and conventional crops are naturally concerned that genetic contamination is hurting acceptance of their products. Three California counties have banned GM crops. Anheuser- Busch Co., the beer giant, has demanded that its home state (Missouri) keep GMO rice fields 120 miles away from rice it buys to make beer. The European Union is now trying to establish buffer zones meant to halt the unwanted spread of GM crops. However, the Wall Street Journal reported November 8 that, "Such moves to restrict the spread of GM crops often are ineffective. Last month in Australia, government experts discovered biotech canola genes in two non-GM varieties despite a ban covering half the country. 'Regretfully, the GM companies appear unable to contain their product," said Kim Chance, agriculture minister for the state of Western Australia, on the agency's Web site.

For some, this seems to come as a shocking revelation -- genetically modified pollen released into the natural environment spreads long distances on the wind. Who would have thought? Actually, almost anyone could have figured this out. Dust from wind storms in China contaminates the air in the U.S. Smoke from fires in Indonesia can be measured in the air half-way around the world. Pollen is measurable in the deep ice of antarctica. No one should ever have harbored any doubt that genetically modified pollen would spread everywhere on the Earth sooner or later. (We are now exactly 10 years into the global experiment with GMO seeds. The first crops were planted in open fields in the U.S. in 1995. From this meager beginning, global genetic contamination is now well along.)Who benefits from all this? Think of it this way: when all crops on earth are genetically contaminated, then the seed companies that own the patented seeds will be in a good position to begin enforcing their patent rights. They have already taken a test case to court and won. In 2004, Monsanto (the St. Louis, Mo. chemical giant) won a seven-year court battle against a 73-year-old Saskatchewan farmer whose fields had been contaminated by Monsanto's genetically modified plants. The Supreme Court of Canada court ruled that the farmer -- a fellow named Percy Schmeiser -- owed Monsanto damages for having Monsanto's patented crops growing illegally in his field.Armed with this legal precedent, after genetically modified crops have drifted far and wide, Monsanto, Dow and the other GMO seed producers will be in a position to muscle most of the world's farmers. It is for cases exactly like this that the U.S. has spent 30 years creating the WTO (world trade organization) -- to settle disputes over "intellectual property rights" (such as patents) in secret tribunals held in Geneva, Switzerland behind closed doors without any impartial observers allowed to attend. Even the results of WTO tribunals are secret, unless the parties involved choose to reveal them. Let me see -- a dirt farmer from India versus Monsanto and Dow backed by the U.S. State Department and the U.S. Treasury. I'm struggling to predict who might win such a politico- legal dispute conducted by a secret tribunal in Geneva, Switzerland.During 2005, it was discovered that GMO crops have not lived up to their initial promise of huge profits for farmers and huge benefits for consumers. It was also discovered that the U.S. Department of Agriculture has not enforced its own strict regulations that were intended to prevent experimental GMO seeds to accidentally contaminating nearby fields. GMO crops were supposed to produce important human health benefits - and the be developed under super- strict government control - but all these promises have turned out to be just so much eye wash.. GMOs were supposed to reduce reliance on dangerous pesticides -- but in fact they have had the opposite effect. Monsanto's first GMO crops were designed to withstand drenching in Monsanto's most profitable product, the weed killer Round-Up -- so farmers who buy Monsanto's patented "Round- up ready" seeds apply more, not less, weed killer.But so what? Who cares if GMO seeds don't provide any of the benefits that were promised? Certainly not the seed companies. Perhaps benefits to the people of the world were never the point. Perhaps the point was to get those first GMO crops in the ground -- promise them the moon! -- and then allow nature to take its course and contaminate the rest of the planet with patented pollen. The intellectual property lawsuits will come along in good time. Patience, dear reader, patience. Unlike people, corporations cannot die, so our children or our grandchildren may find themselves held in thrall by two or three corporations that have seized legal control of much of the world's food supply by getting courts (backed by the threat of force, as all courts ultimately are) to enforce their intellectual property rights.The Danish government has passed a law intended to slow the pace of genetic contamination. The Danes will compensate farmers whose fields have become contaminated, then the Danish government will seek recompense from the farmer whose field originated the genetic contamination, assuming the culprit can be pinpointed. This may slow the spread of genetic contamination, but the law is clearly not designed to end the problem.Yes, it has been a good year for the GMO industry. None of the stated benefits of their products have materialized -- and the U.S. government regulatory system has been revealed as a sham -- but enormous benefits to the few GMO corporations are right on track to begin blossoming. For Monsanto, Dow and Novartis, a decent shot at gaining control over much of the world's food supply is now blowing on the wind and there's no turning back. As the Vice-President of plant genetics for Dow Agrosciences said recently, "There will be come continuing bumps in the road, but we are starting to see a balance of very good news and growth. The genie is way out of the bottle."

Peter Montague is editor of the indispensable Rachel's Health and Democracy, where this essay originally appeared. He can be reached at: peterhttp://www.counterpunch.org/montague01072006.html

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GMOs: New Study Shows Unborn Babies Could Be Harmed

Mortality rate for new-born rats six times higher when mother was fed on a diet of modified soya

 

 

by Geoffrey Lean

 

Published on Sunday, January 8, 2006 by the lndependent/UK

 

 

 

 

Women who eat GM foods while pregnant risk endangering their unborn babies, startling new research suggests.

The study - carried out by a leading scientist at the Russian Academy of Sciences - found that more than half of the offspring of rats fed on modified soya died in the first three weeks of life, six times as many as those born to mothers with normal diets. Six times as many were also severely underweight.

The research - which is being prepared for publication - is just one of a clutch of recent studies that are reviving fears that GM food damages human health. Italian research has found that modified soya affected the liver and pancreas of mice. Australia had to abandon a decade-long attempt to develop modified peas when an official study found they caused lung damage.

And last May this newspaper revealed a secret report ( http://www.commondreams.org/headlines05/0522-03.htm ) by the biotech giant Monsanto, which showed that rats fed a diet rich in GM corn had smaller kidneys and higher blood cell counts, suggesting possible damage to their immune systems, than those that ate a similar conventional one.

The United Nation's Food and Agriculture Organization held a workshop on the safety of genetically modified foods at its Rome headquarters late last year. The workshop was addressed by scientists whose research had raised concerns about health dangers. But the World Trade Organization is expected next month to support a bid by the Bush administration to force European countries to accept GM foods.

The Russian research threatens to have an explosive effect on already hostile public opinion. Carried out by Dr Irina Ermakova at the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, it is believed to be the first to look at the effects of GM food on the unborn.

The scientist added flour from a GM soya bean - produced by Monsanto to be resistant to its pesticide, Roundup - to the food of female rats, starting two weeks before they conceived, continuing through pregnancy, birth and nursing. Others were given non-GM soya and a third group was given no soya at all.

She found that 36 per cent of the young of the rats fed the modified soya were severely underweight, compared to 6 per cent of the offspring of the other groups. More alarmingly, a staggering 55.6 per cent of those born to mothers on the GM diet perished within three weeks of birth, compared to 9 per cent of the offspring of those fed normal soya, and 6.8 per cent of the young of those given no soya at all.

"The morphology and biochemical structures of rats are very similar to those of humans, and this makes the results very disturbing" said Dr Ermakova. "They point to a risk for mothers and their babies."

Environmentalists say that - while the results are preliminary - they are potentially so serious that they must be followed up. The American Academy of Environmental Medicine has asked the US National Institute of Health to sponsor an immediate, independent follow-up.

The Monsanto soya is widely eaten by Americans. There is little of it, or any GM crop, in British foods though it is imported to feed animals farmed for meat.

Tony Coombes, director of corporate affairs for Monsanto UK, said: "The overwhelming weight of evidence from published, peer-reviewed, independently conducted scientific studies demonstrates that Roundup Ready soy can be safely consumed by rats, as well as all other animal species studied."

What the experiment found

Russian scientists added flour made from a GM soya to the diet of female rats two weeks before mating them, and continued feeding it to them during pregnancy, birth and nursing. Others were give non-GM soya or none at all. Six times as many of the offspring of those fed the modified soya were severely underweight compared to those born to the rats given normal diets. Within three weeks, 55.6 per cent of the young of the mothers given the modified soya died, against 9 per cent of the offspring of those fed the conventional soya.

© 2006 Independent News and Media Limitedhttp://www.commondreams.org/headlines06/0108-01.htm

 

 

 

 

 

 

Most Offspring Died When Mother Rats Ate Genetically Engineered Soy

By Jeffrey M. Smith, author of Seeds of Deception

The Russian scientist planned a simple experiment to see if eating genetically modified (GM) soy might influence offspring. What she got, however, was an astounding result that may threaten a multi-billion dollar industry.

Irina Ermakova, a leading scientist at the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences (RAS), added GM soy flour (5-7 grams) to the diet of female rats. Other females were fed non-GM soy or no soy at all. The experimental diet began two weeks before the rats conceived and continued through pregnancy and nursing.

Ermakova’s first surprise came when her pregnant rats started giving birth. Some pups from GM-fed mothers were quite a bit smaller. After 2 weeks, 36% of them weighed less than 20 grams compared to about 6% from the other groups (see photo below).

But the real shock came when the rats started dying. Within three weeks, 25 of the 45 (55.6%) rats from the GM soy group died compared to only 3 of 33 (9%) from the non-GM soy group and 3 of 44 (6.8%) from the non-soy controls.

Ermakova preserved several major organs from the mother rats and offspring, drew up designs for a detailed organ analysis, created plans to repeat and expand the feeding trial, and promptly ran out of research money. The $70,000 needed was not expected to arrive for a year. Therefore, when she was invited to present her research at a symposium organized by the National Association for Genetic Security, Ermakova wrote “PRELIMINARY STUDIES” on the top of her paper. She presented it on October 10, 2005 at a session devoted to the risks of GM food.

Her findings are hardly welcome by an industry already steeped in controversy.

GM Soy’s Divisive Past

The soy she was testing was Monsanto’s Roundup Ready variety. Its DNA has bacterial genes added that allow the soy plant to survive applications of Monsanto’s “Roundup” brand herbicide. About 85% of the soy gown in the US is Roundup Ready. Since soy derivatives, including oil, flour and lecithin, are found in the majority of processed foods sold in the US, many Americans eat ingredients derived from Roundup Ready soy everyday.

The FDA does not require any safety tests on genetically modified foods. If Monsanto or other biotech companies declare their foods safe, the agency has no further questions. The rationale for this hands-off position is a sentence in the FDA’s 1992 policy that states, “The agency is not aware of any information showing that foods derived by these new methods differ from other foods in any meaningful or uniform way.”[1] The statement, it turns out, was deceptive. Documents made public from a lawsuit years later revealed that the FDA’s own experts agreed that GM foods are different and might lead to hard-to-detect allergens, toxins, new diseases or nutritional problems. They had urged their superiors to require long-term safety studies, but were ignored. The person in charge of FDA policy was, conveniently, Monsanto’s former attorney (and later their vice president). One FDA microbiologist described the GM food policy as “just a political document” without scientific basis, and warned that industry would “not do the tests that they would normally do” since the FDA didn’t require any.[2] He was correct.

There have been less than 20 published, peer-reviewed animal feeding safety studies and no human clinical trials—in spite of the fact that millions of people eat GM soy, corn, cotton, or canola daily. There are no adequate tests on “biochemistry, immunology, tissue pathology, gut function, liver function and kidney function,”[3] and animal feeding studies are too short to adequately test for cancer, reproductive problems, or effects in the next generation. This makes Ermakova’s research particularly significant. It’s the first of its kind.

Past Studies Show Significant Effects

Other studies on Roundup Ready soy also raise serious questions. Research on the liver, the body’s major de-toxifier, showed that rats fed GM soy developed misshapen nuclei and other cellular anomalies.[4] This indicates increased metabolic activity, probably resulting from a major insult to that organ. Rats also showed changes in the pancreas, including a huge drop in the production of a major enzyme (alpha-amylase),[5] which could inhibit digestion. Cooked GM soy contains about twice the amount of soy lectin, which can also block nutrient assimilation.[6] And one study showed that GM soy has 12-14% less isoflavones, which are touted as cancer fighting.[7]

An animal feeding study published by Monsanto showed no apparent problems with GM soy,[8] but their research has been severely criticized as rigged to avoid finding problems.[9] Monsanto used mature animals instead of young, more sensitive ones, diluted their GM soy up to 12-fold, used too much protein, never weighed the organs, and had huge variations in starting weights. The study’s nutrient comparison between GM and non-GM soy revealed significant differences in the ash, fat, and carbohydrate content, lower levels of protein, a fatty acid, and phenylalanine. Monsanto researchers had actually omitted the most incriminating nutritional differences, which were later discovered and made public. For example, the published paper showed a 27% increase in a known allergen, trypsin inhibitor, while the recovered data raised that to a 3-fold or 7-fold increase, after the soy was cooked. This might explain why soy allergies in the UK skyrocketed by 50% soon after GM soy was introduced.

The gene that is inserted into GM soy produces a protein with two sections that are identical to known allergens. This might also account for the increased allergy rate. Furthermore, the only human feeding trial ever conducted confirmed that this inserted gene transfers into the DNA of bacteria inside the intestines. This means that long after you decide to stop eating GM soy, your own gut bacteria may still be producing this potentially allergenic protein inside your digestive tract.

The migration of genes might influence offspring. German scientists found fragments of the DNA fed to pregnant mice in the brains of their newborn.[10] Fragments of genetically modified DNA were also found in the blood, spleen, liver and kidneys of piglets that were fed GM corn.[11] It was not clear if the GM genes actually entered the DNA of the animal, but scientists speculate that if it were to integrate into the sex organ cells, it might impact offspring.

The health of newborns might also be affected by toxins, allergens, or anti-nutrients in the mother’s diet. These may be created in GM crops, due to unpredictable alterations in their DNA. The process of gene insertion can delete one or more of the DNA’s own natural genes, scramble them, turn them off, or permanently turn them on. It can also change the expression levels of hundreds of genes. And growing the transformed cell into a GM plant through a process called tissue culture can create hundreds or thousands of additional mutations throughout the DNA.

Most of these possibilities have not been properly evaluated in Roundup Ready soy. We don’t know how many mutations or altered gene expressions are found in its DNA. Years after it was marketed, however, scientists did discover a section of natural soy DNA that was scrambled[12] and two additional fragments of the foreign gene that had escaped Monsanto’s detection.

Those familiar with the body of GM safety studies are often astounded by their superficiality. Moreover, several scientists who discovered incriminating evidence or even expressed concerns about the technology have been fired, threatened, stripped of responsibilities, or censured.[13] And when problems do arise, they are not followed up. For example, animals fed GM crops developed potentially precancerous cell growth, smaller brains, livers and testicles, damaged immune systems, bigger livers, partial atrophy of the liver, lesions in the livers, stomachs, and kidneys, inflammation of the kidneys, problems with their blood cells, higher blood sugar levels, and unexplained increases in the death rate. (See Spilling the Beans, August 2004.) None have been adequately followed-up or accounted for.

Ermakova’s research, however, will likely change that. That’s because her study is easy to repeat and its results are so extreme. A 55.6% mortality rate is enormous and very worrisome. Repeating the study is the only reasonable option.

American Academy of Environmental Medicine Urges NIH to Follow Up Study

I presented Dr. Ermakova’s findings, with her permission, at the annual conference of the American Academy of Environmental Medicine (AAEM) in Tucson on October 27, 2005. In response, the AAEM board passed a resolution asking the US National Institutes of Health (NIH) to sponsor an immediate, independent follow-up of the study. Dr. Jim Willoughby, the Academy’s president, said, “Genetically modified soy, corn, canola, and cottonseed oil are being consumed daily by a significant proportion of our population. We need rigorous, independent and long-term studies to evaluate if these foods put the population at risk.”

Unfortunately, there is a feature about GM crops that makes even follow-up studies a problem. In 2003, a French laboratory analyzed the inserted genes in five GM varieties, including Roundup Ready soybeans.[14] In each case, the genetic sequence was different than that which had been described by the biotech companies years earlier. Had all the companies made a mistake? That’s unlikely. Rather, the inserted genes probably rearranged over time. A Brussels lab confirmed that the genetic sequences were different than what was originally listed. But the sequences discovered in Brussels didn’t all match those found by the French.[15] This suggests that the inserted genes are unstable and can change in different ways. It also means that they are creating new proteins—ones that were never intended or tested. The Roundup Ready soybeans used in the Russian test may therefore be quite different from the Roundup Ready soybeans used in follow-up studies.

Unstable genes make accurate safety testing impossible. It also may explain some of the many problems reported about GM foods. For example, nearly 25 farmers in the US and Canada say that certain GM corn varieties caused their pigs to become sterile, have false pregnancies, or give birth to bags of water. A farmer in Germany claims that a certain variety of GM corn killed 12 of his cows and caused others to fall sick. And Filipinos living next to a GM cornfield developed skin, respiratory, and intestinal symptoms and fever, while the corn was pollinating. The mysterious symptoms returned the following year, also during pollination, and blood tests on 39 of the Filipinos showed an immune response to the Bt toxin—created by the GM corn.

These problems may be due to particular GM varieties, or they may result from a GM crop that has “gone bad” due to genetic rearrangements. Even GM plants with identical gene sequences, however, might act differently. The amount of Bt toxin in the Philippine corn study described above, for example, varied considerably from kernel to kernel, even in the same plant.[16]

With billions of dollars invested in GM foods, no adverse finding has yet been sufficient to reverse the industry’s growth in the US. It may take some dramatic, indisputable, and life-threatening discovery. That is why Ermakova’s findings are so important. If the study holds up, it may topple the GM food industry.

I urge the NIH to agree to the AAEM’s request, and fund an immediate, independent follow-up study. If NIH funding is not forthcoming, our Institute for Responsible Technology will try to raise the money. This is not the time to wait. There is too much at stake.

Click here for press release on Russian rat study.

Click here for the resolution by the American Academy of Environmental Medicine.

Click here for downloadable photos of the rats.

Jeffrey M. Smith is working with a team of international scientists to catalog all known health risks of GM foods. He is the author of Seeds of Deception , the world’s bestselling book on GM food, and the producer of the video, Hidden Dangers in Kids’ Meals.

 

 

 

 

Spilling the Beans is a monthly column available at www.responsibletechnology.org. Publishers and webmasters may offer this article or monthly series to your readers at no charge, by emailing column. Individuals may read the column each month by subscribing to a free newsletter at www.responsibletechnology.org.

 

 

 

 

[1]“Statement of Policy: Foods Derived from New Plant Varieties,” Federal Register vol. 57, no. 104 at 22991, May 29, 1992[2]Louis J. Pribyl, “Biotechnology Draft Document, 2/27/92,” March 6, 1992, www.biointegrity.org[3]Epidemiologist Judy Carman’s testimony before New Zealand’s Royal Commission of Inquiry on Genetic Modification, 2001.[4]Malatesta M, Caporaloni C, Gavaudan S, Rocchi MB, Serafini S, Tiberi C, Gazzanelli G. (2002a) Ultrastructural morphometrical and immunocytochemical analyses of hepatocyte nuclei from mice fed on genetically modified soybean. Cell Struct Funct. 27: 173-180.[5]Manuela Malatesta, et al, Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean, Journal of Anatomy, Volume 201 Issue 5 Page 409 - November 2002[6]Stephen R. Padgette and others, “The Composition of Glyphosate-Tolerant Soybean Seeds Is Equivalent to That of Conventional Soybeans,” The Journal of Nutrition, vol. 126, no. 4, April 1996 (The data was taken from the journal archives, as it had been omitted from the published study.)[7]Lappe, M.A., Bailey, E.B., Childress, C. and Setchell, K.D.R. (1999) Alterations in clinically important phytoestrogens in genetically modified, herbicide-tolerant soybeans. Journal of Medical Food 1, 241-245.[8]Stephen R. Padgette and others, “The Composition of Glyphosate-Tolerant Soybean Seeds Is Equivalent to That of Conventional Soybeans,” The Journal of Nutrition, vol. 126, no. 4, April 1996[9]For example, Ian F. Pryme and Rolf Lembcke, “In Vivo Studies on Possible Health Consequences of genetically modified food and Feed—with Particular Regard to Ingredients Consisting of Genetically Modified Plant Materials,” Nutrition and Health, vol. 17, 2003[10]Doerfler W; Schubbert R, “Uptake of foreign DNA from the environment: the gastrointestinal tract and the placenta as portals of entry,” Journal of molecular genetics and genetics Vol 242: 495-504, 1994[11]Raffaele Mazza1, et al, “Assessing the Transfer of Genetically Modified DNA from Feed to Animal Tissues,” Transgenic Research, October 2005, Volume 14, Number 5, pp 775 - 784[12]P. Windels, I. Taverniers, A. Depicker, E. Van Bockstaele, and M. DeLoose, “Characterisation of the Roundup Ready soybean insert,” European Food Research and Technology, vol. 213, 2001, pp. 107-112[13]Jeffrey M. Smith, Seeds of Deception, Yes! Books, 2003[14] 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 www.i-sis.org.uk[15] http://www.i-sis.org.uk/UTLI.php[16] http://www.seedsofdeception.com/utility/showArticle/?objectID=36

---Source: http://www.seedsofdeception.com/utility/showArticle/?objectID=297

 

 

 

 

 

SENSIBLE REGULATIONS FOR GE FOOD CROPS

 

MORE INFO: http://www.phpbbforfree.com/forums/infonature-about160.html

By David Schubert Source: Nature Biotechnology (23, 785 - 787; July 2005) http://www.nature.com/nbt/journal/v23/n7/full/nbt0705-785b.html In a recent article Bradford and colleagues argued that the methods used to produce food crops should not be the focus of regulatory oversight, only the phenotypic traits of the resultant plants as defined in terms of standard agricultural practice[1]. They propose that any risk and safety assessments of crops produced by genetic engineering (GE) should be based only upon the nature of the introduced genes. They also claim that transgenic crops face a "daunting" array of regulatory requirements. However, safety testing requirements in the United States are largely voluntary and in my view inadequate. These regulations have been reviewed elsewhere[2] and will not be discussed further. Safety concerns related to the GE process itself as well as its unintended consequences are set aside by Bradford et al as irrelevant, for they claim that the products of genetic events that occur naturally and with standard plant breeding techniques are fundamentally the same as those that occur with GE. Are these arguments a valid reflection of what is known about the precision and consequences of the GE process as compared with naturally occurring genomic variation? The basic assumption underlying the concept of a one-to-one relationship between the transgene and the resultant phenotype is that the GE process is relatively precise. However, none of the current transgene insertion techniques permit control over the location of the insertion site or the number and orientation of the genes inserted. Indeed, over one-third of all Agrobacterium-mediated insertion events disrupt functional DNA[3,4]. These and related transformation and cell culture-induced changes in chromosomal structure have been recently documented in great detail[5]. For example, translocations of up to 40 Kb[6], scrambling of transgene and genomic DNA[7], large scale deletions of over a dozen genes[8] and frequent random insertions of plasmid DNA[9] can all be caused by the procedures used to make GE plants. In fact, the most commonly used transformation procedure is sometimes itself used as a mutagen[10], and can activate dormant retrotransposons that are highly mutagenic[11]. Moreover, mutations linked to the transgene insertion site cannot be removed by additional breeding as long as there is selection for the transgene itself. Collectively these data indicate that the GE process itself is highly mutagenic. Some modern breeding technologies introduce new traits into plants via chemical or radiation mutagenesis or by wide cross hybridizations that overcome natural species barriers. Mutagenesis was used in the United States during the middle part of the last century, but food crops made by this technique now constitute less than a few percent of US production, with sunflowers being the major representative[12]. However, plants produced by wide crosses, such as those between quackgrass and bread wheat to yield a widely planted grain that has all of the chromosomes of wheat and an extra half genome of the quackgrass, while unique, are fundamentally different from those produced by either mutagenesis or GE. In wide crosses and other forms of ploidy manipulation there are clearly changes in gene dosage, and proteins unique to only one parent can be produced in the hybrid, but there is no a priori reason to assume that mutations are going to occur simply because there is a change in chromosome or gene number. While the extent and suddenness of all of these modern breeding technologies are unlike anything known to occur during the course of evolution or with traditional breeding, only GE and mutagenesis introduce large numbers of mutations. Any new cultivars derived by the latter two methods should be subjected to similar regulatory requirements. Bradford et al. correctly state that plants normally contain the same Agrobacterium and viral DNA sequences that are used to create GE transfection constructs, but fail to point out that with GE these pieces of DNA are part of a cassette of genes for drug resistance along with strong constitutive viral promoters that are used to express foreign proteins at high levels in all parts of the plant, hardly a natural event. They incorrectly imply that changes in ploidy, gene copy number, recombination, and high genomic densities of transposable elements in normal plants continually lead to mutations and changes in gene expression similar to those caused by GE. Ploidy is notoriously unstable in plants, but changes involve moving around large blocks of intact genes while maintaining their regulated expression pattern. It should also be remembered that recombination is not the same as random mutagenesis, for there has been tremendous selective pressure for alleles to express functionally similar proteins. The statement that "retrotransposons continuously insert themselves between genes" is incorrect, for these high copy number elements are transpositionally inactive in normal modern food plants[13], have evolved and rearranged in the distant past[14], but can be activated by tissue culture or by mutagenesis[11]. In fact their discovery by Barbara McClintock was facilitated by the use of mutagenized corn[13]. While Bradford et al. propose that regulatory efforts should be focused upon the expression of the transgene, I believe that the major hazards of the highly mutagenic plant transformation techniques are the potentials for a decrease in nutritional content or an increase in dangerous metabolites. While it is widely recognized that the breeding of some crops can produce varieties with harmful characteristics, millennia of experience have identified these crops, and breeders test new cultivars for known harmful compounds, such as alkaloids in potatoes[15,16]. In contrast, unintended consequences arising from the random and extensive mutagenesis caused by GE techniques opens far wider possibilities of producing novel, toxic, or mutagenic compounds in all sorts of crops. Unlike animals, plants accumulate thousands of nonessential small molecules that provide adaptive benefits under conditions of environmental or predator-based stress[17]. Estimates are that they can make between 90,000 and 200,000 phytochemicals with up to 5000 in one species[18]. These compounds are frequently made by enzymes with low substrate specificity[19] in which mutations can readily alter substrate preference[20,21] There are many examples of unpredictable alterations in small molecule metabolism in GE organisms. In yeast genetically engineered to increase glucose metabolism, the GE event caused the unintended accumulation of a highly toxic and mutagenic 2-oxoaldehyde called methylglyoxal[22]. In a study of just 88 metabolites in four lines of potatoes transformed for altered sucrose metabolism, Roessner et al. found that the amounts of the majority of these metabolites were significantly altered relative to controls[18]. In addition, nine of the metabolites in GE potatoes were not detected in conventional potatoes. Given the enormous pool of plant metabolites, the observation that 10% of those assayed are new in one set of transfections strongly suggests that undesirable or harmful metabolites may be produced and accumulate[23]. Contrary to the suggestions of Bradford et al., Kuiper and his colleagues strongly recommend that each transformation event should be assayed for these types of unintended events by metabolic profiling[24]. A well documented horticultural example of unintended effects is the alteration in the shikimic acid pathway in Bt corn hybrids derived from Monsanto's MON810 and Syngenta's Bt11 plants as well as glyphosate-tolerant soybeans. Stem tissue of both groups of plants has elevated levels of lignin, an abundant non-digestible woody component that makes the plants less nutritious for animal feed[25,26]. Components of this same biochemical pathway also produce both flavonoids and isoflavonoids that have a high nutritional value, and rotenone, a plant-produced insecticide that may cause Parkinson's disease[27]. Isoflavonoids are abundant in legumes like soy beans, and rotenone is synthesized directly from isoflavones in many legume species[28]. Because of the promiscuity of many plant enzymes and the large and varied substrate pools of phytochemical intermediates, it is impossible to predict the products of enzymes or regulatory genes mutated during the GE event[23]. While I are not aware of any testing of GE soybeans for rotenone, it has been shown that glyphosate-tolerant soybeans sprayed with glyphosate have a reduced flavonoid content[29]. The safety testing of GE crops need not be as extensive as that done with drugs, food additives or cosmetics. Many suggestions have been put forward (see, for example 30,2,5,24) including those by the World Health Organization[31]. I believe that the most important safety tests include metabolic profiling to detect unexpected changes in small molecule metabolism[24] and the Ames test to detect mutagens[32]. Molecular analysis of the gene insertion sites and transformation-induced mutations[5] should also be performed along with both multigenerational feeding trials in rodents to assay for teratogenic effects and developmental problems, and allergenicity testing performed according to a single rigorous protocol[31] The animal studies are of particular importance for crops engineered to produce precursors to highly biologically active compounds such as Vitamin A and retinoic acid, molecules that can act as teratogens at high doses[33]. In summary, Bradford et al. state that there is a low risk from the consumption of GE plants "where no novel biochemical or enzymatic functions are imparted". The question is, of course, how can one know if a novel and potentially harmful molecule has been created unless the testing has been done? How can one predict the risk in the absence of an assay? Because of the high mutagenicity of the transformation procedures used in GE, the assumptions made by Bradford et al. and also the FDA [34] about the precision and specificity of plant GE are incorrect. Nonetheless, it appears that the positions of Bradford et al. and the biotech industry, as well as the current regulatory framework for the labeling and safety testing of GE food crops, is to maintain the status quo and hope for the best. The problem is that there are no mandatory safety testing requirements for unintended effects[2] and that it may take many years before any symptoms of a GE-caused disease appear. In the absence of strong epidemiology or clinical trials, any health problem associated with an illness caused by a GE food is going to be very difficult, if not impossible, to detect unless it is a disease that is unique or normally very rare. Therefore, while GE may be able to enhance world health and food crop production , its full potential is likely to remain unfulfilled until rigorous pre-release safety testing can provide some assurance to consumers that the products of this new technology are safe to eat. REFERENCES: 1. Bradford, K. J., Van Deynze, A., Gutterson, N., Parrott, W. & Strauss, S. H. Regulating transgenic crops sensibly: lessons from plant breeding, biotechnology and genomics. Nat Biotechnol 23, 439-44 (2005). 2. Freese, W. & Schubert, D. Safety testing of genetically engineered food. 21 Biotechnology and Genetic Engineering Reviews, 299-325 (2004). 3. Szabados, L. et al. Distribution of 1000 sequenced T-DNA tags in the Arabidopsis genome. Plant J 32, 233-42 (2002). 4. Forsbach, A., Schubert, D., Lechtenberg, B., Gils, M. & Schmidt, R. A comprehensive characterization of single-copy T-DNA insertions in the Arabidopsis thaliana genome. Plant Mol Biol 52, 161-76 (2003). 5. Wilson, A., Latham, J. & Steinbrecher, R. 35 (EcoNexus, Brighton, UK, 2004). 6. Tax, F. E. & Vernon, D. M. T-DNA-associated duplication/translocations in Arabidopsis. Implications for mutant analysis and functional genomics. Plant Physiol 126, 1527-38 (2001). 7. Makarevitch, I., Svitashev, S. K. & Somers, D. A. Complete sequence analysis of transgene loci from plants transformed via microprojectile bombardment. Plant Mol Biol 52, 421-32 (2003). 8. Kaya, H. et al. Hosoba toge toge, a syndrome caused by a large chromosomal deletion associated with a T-DNA insertion in Arabidopsis. Plant Cell Physiol 41, 1055-66 (2000). 9. Kim, S. R. et al. Transgene structures in T-DNA-inserted rice plants. Plant Mol Biol 52, 761-73 (2003). 10. Weigel, D. et al. Activation tagging in Arabidopsis. Plant Physiol 122, 1003-13 (2000). 11. Hirochika, H., Sugimoto, K., Otsuki, Y., Tsugawa, H. & Kanda, M. Retrotransposons of rice involved in mutations induced by tissue culture. Proc Natl Acad Sci U S A 93, 7783-8 (1996). 12. Ahloowalia, B. S., Maluszynski, M. & Nichterlein, K. Global impact of mutation-derived varieties. Euphytica 135, 187-204 (2004). 13. Feschotte, C., Jiang, N. & Wessler, S. R. Plant transposable elements: where genetics meets genomics. Nat Rev Genet 3, 329-41 (2002). 14. Brunner, S., Fengler, K., Morgante, M., Tingey, S. & Rafalski, A. Evolution of DNA Sequence Nonhomologies among Maize Inbreds. Plant Cell 17, 343-60 (2005). 15. Korpan, Y. I. et al. Potato glycoalkaloids: true safety or false sense of security? Trends Biotechnol 22, 147-51 (2004). 16. Ewen, S. W. & Pusztai, A. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet 354, 1353-4 (1999). 17. Verpoorte, R. in Metabolic Engineering of Plant Secondary Metabolism (eds. Verpoorte, R. & Alfermann, A. W.) 1-29 (Kluwer Academic Publishers, Dordrecht , The Netherlands, 2000). 18. Roessner, U. et al. Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems. Plant Cell 13, 11-29 (2001). 19. Schwab, W. Metabolome diversity: too few genes, too many metabolites? Phytochemistry 62, 837-49 (2003). 20. Zubieta, C. et al. Structural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family. Plant Cell 15, 1704-16 (2003). 21. Johnson, E. T. et al. Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4-reductase. Plant J 25, 325-33 (2001). 22. Inose, T. & Murata, K. Enhanced accumulation of toxic compound in yeast cells having high glycolytic activity: A case study on the safety of genetically engineered yeast. Intl J Food Sci Tech 30, 141-6 (1995). 23. Grotewold, E. Plant metabolic diversity: a regulatory perspective. Trends Plant Sci 10, 57-62 (2005). 24. Kuiper, H. A., Kleter, G. A., Noteborn, H. P. & Kok, E. J. Assessment of the food safety issues related to genetically modified foods. Plant J 27, 503-28 (2001). 25. Saxena, D. & Stotzky, G. Bt corn has a higher lignin content than non-Bt corn. Amer J Botany 88, 1704-6 (2001). 26. Gertz, J. M., Vencill, W. K. & Hill, N. S. in Proceedings of the 1999 Brighton Crop Protection Conference: Weeds 835-840 (British Crop Protection Council, Farnham, UK, 1999). 27. Betarbet, R. et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci. 3, 1301-1306 (2000). 28. Morgan, E. D. & Wilson, I. D. in Comprehensive Natural Products Chemistry (ed. Mori, K.) 363-375 (Pergamon Press/Elsevier Science, Oxford, 1999). 29. Lappe, M. A., Bailey, E. B., Childress, C. & Setchell, K. D. R. Alterations in clinically important phytoestrogens in genetically modified, herbicide-tolerant soybeans. J Med Foods 1, 241-245 (1999). 30. Edmonds_Institute. Manual for assessing ecological and human health effects of genetically engineered organisms. http://www.edmonds-institute.org/manual.html. (Edmonds Institute, 1998). 31. FAO-WHO. Evaluation of Allergenicity of genetically modified foods. Report of a Joint FAO/WHO expert consultation on allergenicity of foods derived from biotechnology. January 22-25, 2001. http://www.fao.org/es/ESN/food/pd/allergygm.pdf. (2001). 32. Maron, D. M. & Ames, B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res 113, 173-215 (1983). 33. McCaffery, P. J., Adams, J., Maden, M. & Rosa-Molinar, E. Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen. Eur J Neurosci 18, 457-72 (2003). 34. Kessler, D. A., Taylor, M. R., Maryanski, J. H., Flamm, E. L. & Kahl, L. S. The safety of foods developed by biotechnology. Science 256, 1747-9, 1832 (1992).