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For a successful technology
Reality must take precedence over public relations,
for nature cannot be fooled.
-Richard Feynman

Nobel physicist Richard Feynman was talking about the role NASA and its industrial partners played in the 1986 Challenger disaster, but his words could easily apply to the debate over genetically modified (GM) crops. When grain processor Archer Daniels Midland (ADM) of Decatur, Ill., asked suppliers on Sept. 2 to segregate GM corn from traditional varieties, some U.S. biotechnologists probably wondered if it was the beginning of the end for crops that already cover an area larger than the United Kingdom. ADM's move followed a European blockade of imported GM foods and a growing trickle of American companies banning GM ingredients from their products. Has the near panic in Europe over GM foods leaped the Atlantic? How can science be separated from hype to make sense of the actual risks in GM foods?

"It's becoming an epidemic. If large end users stop accepting a product, it is going to dampen the entire pipeline. There will be fewer gene-spliced crops grown, and less research and development," maintains Henry Miller, former director of the Office of Biotechnology at the Food and Drug Administration (FDA) and currently a research fellow at the Hoover Institution of Stanford University.

With certain environmental groups not-so-subtly catalyzing the antitechnology movement, much of the public is unaware that evidence that FM foods are unsafe is so far nonexistent, and that the products hold enormous promise for feeding a burgeoning human population. "There is no science to back up the reasons for concern about foods from GM plants at all. Hundreds of millions of people have eaten GM foods, and no one has ever gotten sick," says Peter Raven, director of the Missouri Botanical Garden in St. Louis. Raven is backed by the Food Safety Authority of Ireland, which thinks there's "no reason to believe that GM foods currently on the market in the 15-member European Union are any less safe than their traditional counterparts."[1]

Rampant fear of GM foods in Europe, especially the United Kingdom, is rooted in recent history - specifically, the British government's downplaying bovine spongiform encephalopathy (BSE, or "made cow disease") in the mid-1900s. The notorious British media fanned the flames of mistrust, and statements such as Prince Charles' opinion that genetic manipulation "takes mankind into realms that belong to God and to God alone" did not help. In June 1999, environmental ministries from the European Union placed a moratorium on importing GM foods new regulations are in place-which may not be until 2002.

On July 12, U.S. Secretary of Agriculture Dan Glickman, speaking to the National Press Club, tried to head off a trade war by reassuring the public of the safety and promise of GM foods, calling for such safeguards as long-term monitoring and labeling. Yet he also acknowledged the power of consumer choice, stating that an "if you you grow it they will come" mindset simply will not work.

His words rang true weeks later when Gerber Food Products led the way in announcing that it would discontinue using mixed grains that could contain GM corn or soybeans in dry baby cereal - even though parent company Novartis AG of Basel, Switzerland, is a biotech leader and markets B1 corn, which contains a gene encoding an insecticide form the bacterium Bacillus thuringiensis [2]. In doing so, Gerber initiated a doublespeak mantra of sorts, schewing GM foods while pronouncing their safety. "Gerber and Novartis agree that genetically modified organisms are completely safe. It is a question of consumer preference, not safety," says Bryant Haskins, director of media and financial communications at Novartis.

But the move sent a message both to consumers and to industry. In the weeks to come, Heinz and Nestle replaced the "Gerber" in Haskins' statement. Then Dayton, Ohio-based pet food giant Iams ousted GM grains, removing a market for U.S. GM products turned away from Europe. A chain reaction had begun. On Aug. 29, two major breweries in Japan and a top tortilla producer in Mexico announced plans to avoid GM corn. In light of these developments, the ADM move wasn't surprising. U.S. farmers, who have heartily embraced GM crops since 1996, were advised by the American Corn Growers Association to consider planting only non-GM corn next year.

Gerber executives insist that the company's decision evolved from an ongoing investigation into anti-GM sentiment in Europe. But others, speaking on the condition of anonymity, said that Greenpeace intentionally flung the first volley by targeting U.S. baby food manufacturers, playing on the powerful emotions associated with harming children. "Greenpeace examined Gerber cereal, and the results were published in the (Lost Angeles) Times," reports Jan Relford, senior vice president of research, product development, and quality assurance for Gerber's research division in Fremont, Mich. The company confirmed Greenpeace's finding of traces of GM corn and soybean in the cereal, decided to substitute more expensive alternate sources, and told a reporter from the Wall Street Journal of the action. They did not issue a news release.

Redford explains the reasoning. "We decided not to highlight a biotechnology product for our consumers. We would market and distribute a product with genetically enhanced materials if we could see a consumer benefit - such as a carrot that produces excess vitamin A. We are being held up to fighting the genetically enhanced war, and we just don't want to fight that fight. These were just minor ingredients, so it wasn't an issue."

But miller maintains that Gerber's decision is very much an issue, calling such moves by several companies "cowardly capitulation" to consumer hysteria.

Ironically, Britons have been eating GM foods for some time, product success apparently rooted in packaging and perception. Consider "Chymogen," a cheese manufactured using the enzyme chymosin, usually of bovine origin, produced in recombinant yeast. "Because the chymosin no longer came from suckling calf stomachs-Britons are quite fond of their suckling calves- it was introduced as a vegetarian cheddar in 1991. And the vegetarian organizations adopted it enthusiastically. One supermarket added a label saying the cheese was produced using gene technology, and the sales did not go down." reported John A. Bryant, a geneticist at the University of Exeter's Washington Singer Laboratory in Exeter. United Kingdom, at the Sixteenth International Botanical Congress in Botanical Congress in St. Louis in August. Ditto for tomato paste. "The media tried to make a big deal that the product had been foisted on the public, but the introduction was almost without notice. It easily outsells non-GM tomato products because it is cheaper. They have labels too," he adds.

But once young people began dying of BSE in 1994, public fear of GM foods in the United Kingdom mushroomed, even though the outbreak had nothing to do with gene technology. "Today public opinion is so strong against genetic engineering in food product that almost all the supermarkets have removed GM foods from their shelves," David Cove, professor of genetics at the University of Leeds, told the botanical congress. He and his students surveyed 500 adults in the United Kingdom, concluding that fear is fueling the anti-GM sentiment. "People have a fear of eating DNA! We eat 150,000 kilometers of DNA in an average meal," he said.

Part of the barrier separating consumers and scientists concerning GM foods is a misunderstanding of risk. Consumers demand absolute assurances, but science deals with uncertainty. "Is the fear justified? That is the heart of the debate. Are there risks in GM foods? Scientists get into trouble, because they say yes, there is risk. There is risk in every single activity that humans do," says Cove. Iain Taylor, a professor of botany at the University of British Columbia, agrees. "Botanists have been caught off guard at the public response to the spin doctoring of the technology. The public perceives that scientists respond that the danger is not real, or the benefits too great to be ignored, and we'll deal with any problems if and when they arise."

Despite scientists' image problem, most don't gibly dismiss possible risks of GM crops. Taylor cites several: the instability of DNA; the degree to which laboratory and field tests mimic reality; whether pollinators spread altered genomes to weeds; and the impact of GM crops on plummeting biodiversity. But many of these concerns also apply to traditional agriculture. Conventional breeding can induce production of natural toxins or move disease resistance genes from wild relatives into crop plants.

A big problem in public acceptance of GM foods is that evidence for safety is negative evidence, not easily explained or published, either in the scientific literature or tabloids. There is always the possibility, no matter how slim, that something could go wrong. So advocates are quick to invoke the "what if" argument: "We don't know for sure, we can't prove that there's no danger." Science deals in probabilities, but the public has little appreciation for P values, so the few studies purporting specific risks have received disproportionate media play.

Consider two oft-described studies - one on Brazil nuts, the other on monarch butterflies:

In 1996, Pioneer Hi-Bred International commissioned a research team from the University of Nebraska to investigate whether canola and beans given an albumin-encoding gene from Brazil nuts was allergenic to nine volunteers with known Brazil nut allergy.[3] The genetic manipulation aimed to add methionine to the protein content of the crops, slated for use as animal feed. When seven of the volunteers reacted, the company immediately halted the program. News reports focused on the potentially deadly combination of lack of labels and allergic reactions. Yet the study also showed how the regulatory system identifies and addresses risks.

The monarch butterfly, thanks to a one-page report, is now a poster organism for the anti-GM movement. a team led by John Losey of Cornell University fed milkweed leaves dusted with pollen from a Novartis Bt corn hybrid to monarch butterfly caterpillars.[4] Bt toxin kills European corn borer and corn ear worm. Nearly 45 percent of the caterpillars died, and survivors were scrawny. But as soon as the study appeared many scientists challenged the methodology and relevance to field conditions. Others appealed for perspective - far more monarchs are killed by habitat destruction in Mexico and truck traffic on corn belt highways. Transgenic Bt also reduced the use of pesticides, according to the U.S. Department of Agriculture's Economic Research Service.[5] Still, Raven says that from talking to journalists, he appreciates the impact of the monarch study. "It was easy-to-understand unexpected consequence of a GM crop. On one expected corn pollen to coat plants."

Antibiotic Resistance Markers

Although the nut and butterfly cases were based on objective testing, unsubstantiated fear is also part of the mix, judging from arguments that antibiotic resistance genes used to screen transgenics can be transferred from plants to disease-causing bacteria. "Novartis' Bt maize contains genes for antibiotic resistance, which ... should be excised, due to the possibility of causing antibiotic resistance in the animals [that] would be fed on it," says Helen Wallace, senior scientist for Greenpeace in the United Kingdom.

But that possibility is vanishingly small, and may be irrelevant given the widespread nature of antibiotic resistance, which is due more to overprescription of drugs [6] and the wholesale use of antibiotics in animal feed than decreases-old marker genes, according to Abigail Salyers, professor of microbiology at the University of Illinois, Urbana. Because there are no known cases of such resistance transfer in nature, and experimental data are limited and laboratory based, she did the next best thing- a risk analysis based on the genetic events that would have to transpire for the feared scenario to occur.[7]

"It would take a series of extremely improbable steps-the looping out of (the resistance gene), its introduction into enteric bacteria, and its stable maintenance are extremely unlikely to occur," Salyers concludes. Even if transfer from plants to bacteria did occur, "it would be a tiny blip, like a teaspoon of water in the ocean," compared to the larger problem of resistance arising from antibiotics in animal feed. Besides, she adds, "from a clinical perspective, it's a nonevent, because ... the old genes (resistance markers) have been superseded by new resistance genes."

Salyers worries that concern about marker genes is out of proportion to their probable danger. And a July 1999 meeting sponsored by the Centers for Disease Control and Prevention (CDC) in Atlanta supported that view. At the meeting, scientists and regulators from government, industry, and the medical profession considered steps to combat antibiotic resistance. While not discounting the danger of transfenic markers, J. Todd Webber, senior medical officer at CDC who helped organize the meeting, admitted that "maybe somebody brought it up, but I'm fairly certain it didn't end up as an action item."

Antibiotic resistance may soon be a non-issue in biotech for another reason. Says University of Nebraska plant pathologist Anne Vidaver, "As a matter of policy, companies are trying to phase out the markers," Other approaches can substitute. For example, a group led by Nam-hai Chua of Rockefeller University and the University of Singapore reported a selectable gene for an enzyme that increases levels of a growth-promoting plant hormone.[8]

Herbicide-Resistant 'Superweeds'

Farmers have flocked to glyphosate-resistant (Roundup Ready) soybeans and corn. As other crops are armed with the gene, resistance could move into weedy relatives. In contrast to antibiotic resistance markers, however, substantive science backs concerns about glyphosate and glufosinate. Genese flow into hybrids between weeds and crops such as canola, squash, sunflower, and sugar beet. [9, 10] According to Ian Heap, director of WeedSmart,. an herbicide-resistance research organization funded by the Weed Science Society of America and two industry-related groups- the North American Herbicide-Resistance Working Group and the Herbicide Resistance Action Committee-- "the probability of problems arising for most crops, including corn and soybean, is extremely low. On the other side, if people were to genetically engineer herbicide-resistant oats, then there would be an immediate problem, as they would cross with wild oats in the first year of release and create herbicide-resistant wild oats." Canola is somewhat in the middle, he adds. Hybrids between transgenic canola, rapeseed, and their wild mustard relatives express herbicide resistance genes and with successive backcrossing, the genes persist in plants that look more and more like the original weeds. [11, 12, 13].

But scientists disagree on the significance of such gene flow. While Rikke Jorgensen's group at the Riso National Laboratory in Denmark detected herbicide tolerance in wild mustardlike plants, following hybridization, [11] other studies showed that the risk of spread is low. [12, 13] It's also unclear if the genes confer any advantage to weeds in the absence of selection pressure (in the form of herbicide that would make them more invasive or fit, thereby altering ecosystems. As with antibiotic resistance, the absence of selection pressure means that resistance genes should eventually be lost.

Without evidence showing that spread of resistance transgenes is really a problem, much of the concern is still "what if" realm. And once again, the debate could profit from a bit of perspective. Says U.K.'s Royal Society in a comprehensive report on transgenic plants, "It is also notable that disease and pest-resistant crops have been available for many years as a result of conventional breeding techniques, and we are not aware of any reported problems as a result of transfer of such traits." [14] WeedSmart's ongoing survey of herbicide resistance lists 216 cases in 45 countries, but apparently none from transgenes.[15] Because spontaneous resistance to glyphosate is so rare, spread of resistance via a transgene should be easy to spot.

If scientific evidence warranting concern over transgenic plants is minimal, why all the fuss? Why has fear overtaken reason in the debate over GM foods? A Perspective explores these questions.

REFERENCES

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1. Food Safety Authority of Ireland. "Food safety and genetically modified foods," May 1999., ww.fsai.ie

2. B.A. Palevitz, "Bt or not Bt ... transgenic corn vs monarch butterflies, " The Scientist, 13(12):1, June 7, 1999.

3. J.A. Nordlee et al., "Identification of a Brazil-nut allergen in transgenic soybeans," New England Journal of Medicine, 334: 688-92, 1996.

4. J.E. Losey et al., "Transgenic pollen harms monarch larvae," Nature, 399: 214, May 20, 1999.

5. Economic Research Service, U.S. Department of Agriculture, "Impacts of adopting genetically engineered crops in the U.S.-preliminary results," July 20, 1999, www.econ.ag.gov/whatsnew/issues/gmo

6. R. Gonzalez, "Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians," JAMA: The Journal of the American Medical Association, 278: 901-4, 1997. Also see editorial comment on page 944.

7. A. Salyers, "Genetically engineered foods: safety issues associated with antibiotic resistance genes," www.healthsci.tufts,edu/apua/salyersreport.htm

8. T. et al., "Inducible isopentenyl transferase as a high efficiency marker for plant transformation," Nature Biotechnology, 17: 916-9, September 1999.

9. A.F. Raybould, A.J. Gray, "Will hybrids of genetically modified crops invade natural ecosystems?" Trends in Ecology and Evolution, 9: 85-9, 1994.

10. A.J. Gray, A.F. Raybould, "Reducing transgene escape routes," Nature, 392: 653-4, 1998.

11. T.R. Mikkelsen et al., "The risk of crop transgene spread, " Nature, 380:31, 1996.

12. A.M. Chevre et al., "Gene flow from transgenic crops," Nature, 389:924, 1997.

13. S.E. Scott, M.J. Wilkinson, "Transgene risk is low," Nature, 393: 320, 1998.

14. The Royal Society, "Genetically modified plants for food use," 1998. www.royalsoc.ac.uk/st_pol40.htm#enviro

Updated: Thursday, September 6, 2007.