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Date:

September 1, 2009

Subject:

German Experts OK on Bt Maize; Rice Fragrance Gene; Where's the Super Food?; GM Crops: Battlefield; Condoms from Dandelions

 


* German Biosafety Committee Statement on MON810 Bt Maize
* Dandelions Engineered for Natural Latex Production
* Highly Valued Rice Fragrance Has Origins In Basmati Rice, Study Finds
* Where's the Super Food?
* GM Crops: Battlefield

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German Biosafety Committee Statement on Bt Maize - the scientific arguments used in the German safeguard clause on MON810 (English translation):

http://www.bvl.bund.de/cln_027/nn_1209020/EN/06__Genetic__Engineering/ZKBS/01__Allg__Stellungnahmen/05__plants/zkbs__mon810__engl.html


Summary: The German Central Committee on Biological Safety (ZKBS) has taken the cultivation ban on Bt maize MON810 of April 2009 as an opportunity to review its risk assessment of the cultivation of Bt maize MON810 of 2007 and to subject six new studies on the impact of Bt maize on non-target organisms to a detailed assessment. These studies mostly comprise laboratory test and have partially been drawn on as decisive factors for the cultivation ban on MON810 ordered by the BMELV (Federal Ministry of Food, Agriculture and Consumer Protection). The studies have been conducted by Rosi-Marshall et al. (2007), Bøhn et al. (2008), Kramarz et al. (2007), Schmidt et al. (2009), Hofmann (2007) and Hofmann et al. (2009).

A scientific assessment of the study results has revealed that none of them confirm potential adverse effect on non-target organisms by MON810 under cultivation conditions. The assessment is also considering the fact that some of the studies are of scientifically lower quality. The conclusion of the ZKBS is in line with the expert assessment of a French author group (Ricroch et al., 2009) and the opinion of the EFSA (European Food Safety Authority) on the request for renewal MON810 (EFSA, 2009). Both documents regard the German ban as scientifically not justified.

The ZKBS states that the cultivation of MON810 has no adverse effect on the environment.

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Dandelions Engineered for Natural Latex Production

- Med Gadget, September 1, 2009 http://www.medgadget.com

Researchers from the Fraunhofer Institute for Molecular Biology and Applied Ecology in Aachen, Germany have genetically modified a dandelion species to produce natural latex that doesn't immediately polymerizes when exposed to air. This can lead to large scale production of natural latex that, so far, has not been shown to cause allergies in people. If the plants prove themselves viable for agriculture, they may supplant synthetic latex altogether for medical applications.

“We have identified the enzyme responsible for the rapid polymerization and have switched it off,” says Prof. Dr. Dirk Prüfer, Head of Department at the IME. “If the plant is cut, the latex flows out instead of being polymerized. We obtain four to five times the amount we would normally. If the plants were to be cultivated on a large scale, every hectare would produce 500 to 1000 kilograms of latex per growing season.” The dandelion rubber has not caused any allergies so far, making it ideal for use in hospitals.

In the lab the researchers have genetically modified the dandelion. Their next step will involve cultivating the optimized plants using conventional breeding techniques. In around five years, Prüfer estimates, they may well have achieved their goal. In any case, the dandelion is not just suitable for rubber production: the plant also produces substantial quantities of inulin, a natural sweetener.

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Highly Valued Rice Fragrance Has Origins In Basmati Rice, Study Finds

- Krishna Ramanujan, September 2, 2009 http://www.cornell.edu/

A new Cornell study reports that the gene that gives rice its highly valued fragrance stems from an ancestor of basmati rice and dispels other long-held assumptions about the origins of basmati.

Rice is classified into two major varietal groups: Japonica and Indica , both of which were grown in China some 8,000 years ago and are believed to have originated from there. The new study, published Aug. 25 in the Proceedings of the National Academy of Sciences, confirms that basmati rice, long assumed to be an Indica variety, is actually more closely related genetically to Japonica rice.

Basmati, which is endemic to northern India, Pakistan and Iran, has been falsely assumed to be in the Indica group due to its characteristic long, thin grains and because it is grown in India, where Indica varieties are widespread. Japonica varieties, which include sushi rice, are widely grown in East and Southeast Asia and tend to have shorter, stickier grains.

When the gene, called BADH2, loses its function through the natural process of mutation, rice becomes fragrant. This study reports eight novel mutations in BADH2 associated with fragrance and found that a previously discovered mutation, or allele, is shared by the vast majority of fragrant rice varieties today, including the fragrant Japonica varieties known as basmati and the fragrant Indica variety known as Thai jasmine.

Through genetic analysis of the DNA flanking BADH2, the researchers determined that the major fragrance allele originated in a Japonica-ancestor of basmati rice and was later transferred to Indica varieties, including Thai jasmine rice. People think that all rice [varieties] in India are from the Indica varietal group, but that's not true," said Susan McCouch, professor of plant breeding and genetics and the paper's senior author. Michael Kovach, a doctoral student in McCouch's lab, is the paper's first author.

The new study supports findings from a 2005 paper by McCouch that showed the close genetic relationship of basmati rice to the Japonica varietal group. "India has both Indica and Japonica rice," McCouch added. "Basmati is a unique type of rice but it is genetically more closely related to sushi rice from Japan than to many of the long grained Indica rices grown elsewhere in India. It is intriguing to think about what these relationships tell us about human migration and cultural exchange."

The findings have important implications for claims of ownership of rice varieties and traits, said Kovach. Rice fragrance is one of the most highly valued traits of rice, and it can command higher prices on the global market. Thai scientists recently patented the use of a genetic engineering strategy to knock out the BADH2 gene while claiming the fragrance trait was part of their national heritage -- through Thai jasmine rice -- and "belonged to the Thai people," Kovach said. "They would like to use this approach to impart this characteristic fragrance on other crops like wheat and maize," Kovach added. "There was no proof that the common BADH2 allele causing fragrance in Thai jasmine rice actually did not originate in jasmine varieties, until this study."

"The results suggest something profound and interesting about human culture, and that is, we are all hybrids," said McCouch. "Claims of ownership of rice are important for national identity, but people's concepts of national identity are often over-simplified. Humans continuously exchange ideas, technology and everything that is valuable, and in the exchange, they become something new. The lesson is that while each culture and each rice variety represents something unique, much of what we value most is shared by all."

The study was funded by the Plant Genome Program of the National Science Foundation and the European Union Project METAPHOR.

=================

Where's the Super Food?

- Bob Grant, The Scientist, Vo. 23, p 30. Full article at http://www.the-scientist.com/article/print/55926/

Watch the related video at http://www.youtube.com/watch?v=Vxt52pUYROg

Scientists have genetically engineered several biofortified food plants to tackle a scourge of developing countries—micronutrient malnutrition. The crops have yet to be planted on a wide scale, but that may be about to change.

Right now, one billion people are starving. That’s one in every six people on this planet. The number of these hungry people is roughly equivalent to the populations of the United States, Indonesia, Brazil, Pakistan, and Bangladesh combined.

The world reached this bleak milestone in the middle of June this year. With the global human population continuing to explode and resources being stripped at an increasing rate, the outlook is not good. More people will go hungry. Less will have access to the nutrients their bodies need. And more will succumb to the illnesses that take advantage of the malnourished body. More people will die.

But this is only half the story. The insidious corollary to the global hunger crisis is that even more people—at least half the world’s population, according to a 2004 United Nations report—suffer from micronutrient malnutrition. People suffering from this “hidden hunger” may consume sufficient calories, but lack suitable amounts of essential nutrients, vitamins, and minerals. These legions of nutrient-starved people largely reside in developing countries. Their plight is dire. Even mild micronutrient deficiencies can increase infant mortality rates and lead to cognitive impairment and immune system problems in children, among other serious health issues.

In addressing global hunger and micronutrient malnourishment, biotechnology holds potential solutions: specifically, nutritionally enhanced, transgenic crops. The technology that makes these plants possible took center stage in January 2000 with the publication of a brief but high-impact Science paper on the creation of a prototype that would become known as “Golden Rice,” packed with beta-carotene (also called pro-vitamin A), the precursor to vitamin A and an essential component of healthy diets.1 Genetically modified (GM) crop plants were already becoming commonplace, but existing genetic changes mostly endowed plants with desirable producer traits, such as herbicide or pest resistance in soybeans or cotton plants. To create Golden Rice, European scientists, with funding from the Rockefeller Foundation, inserted bacterial transgenes into the latent pro-vitamin A biosynthesis molecular pathways in wild-type rice, which contains no pro-vitamin A. This modification transformed the normally nutrient-poor endosperm—or kernel—of milled rice into a source of beta-carotene.

Their work was trumpeted on the cover of TIME magazine with the headline: “This rice could save a million kids a year,” preventing night blindness and other disorders caused by low vitamin A, a nutrient often lacking in developing world diets. While it got people talking and thinking about the potential of genetic engineering to salve the world’s hunger pangs, Golden Rice also set up a contentious debate that still rages today. “[Golden Rice] was something that attracted the attention of both opponents and proponents in the same way,” recalls Peter Beyer, a plant biochemist at the University of Freiburg in Germany and one of Golden Rice’s inventors.

Nutritionists took Beyer and his co-inventor, now-retired biologist Ingo Potrykus, to task, pointing out that Golden Rice could do little to address vitamin A deficiencies in the developing world because its beta-carotene content was too low. Beyer says that anti-GM groups “hijacked” the issue and used Golden Rice as a springboard to rail against all GM crops. Largely due to this controversy, along with political and technological obstacles, nearly 10 years after it was unveiled, Golden Rice has yet to make its wide debut in the paddies of the developing (and vitamin A–deficient) world. “Once [the science] is there, your initial belief is that your work is done, but by far it is not,” says Beyer.

But Beyer, Potrykus, and several collaborators have continued to forge on, refining the technology that made Golden Rice possible and amassing a larger consortium to try to get the enhanced staple crop into the dinner bowls of the people who most need it. And the failure of Golden Rice to leap directly into the world’s rice paddies has not dissuaded scientists from trying the same with other enhanced crops: carrots with twice the calcium, tomatoes with 20% more antioxidants, cassava boosted with additional iron, protein, and vitamins. There are dozens of reports in the scientific literature of common food plants that have been engineered to produce increased levels of one nutrient or another. One cannot yet find vast paddies of Golden Rice waving in the tropical sun or fields of super-cassava blanketing African farmland, but this may be about to change.

More than 250 million sub-Saharan Africans rely on the cassava, a starchy tuber native to South and Central America, as their staple food. Cassava supplies 38.6% of the caloric requirements in some parts of Africa, where hunger and nutrient deficiencies grip the populace and more than 40% of global cassava production takes place.

But cassava is not a particularly nutrient-rich food. It lacks much of the iron, zinc, and vitamins A and E that healthy bodies need to grow. University of Nebraska–Lincoln biochemist Ed Cahoon has worked for several years as part of the BioCassava Plus program, which aims to improve the nutritional profile of cassava through genetic engineering.

Launched in July 2005 with $7.5 million from the Bill and Melinda Gates Foundation’s Grand Challenges in Global Health Initiative, the program’s overarching goal is to develop what essentially amounts to a super-charged cassava plant variety—one with increased levels of iron, zinc, protein, vitamins, and resistance to the cassava mosaic and brown streak viruses plaguing African farmers.

The program has started by developing separate GM cassavas with each of these nutritional improvements one by one. Cahoon and his colleagues have produced a beta-carotene–enhanced cassava by inserting genes that impart higher levels of the pro-vitamin (and give an orangey glow to the normally pallid root). They inserted a gene called phytoene synthase (psy) originally derived from the soil bacterium Erwinia herbicola (and also used to develop Golden Rice), which codes for an enzyme that catalyzes a crucial step in the beta-carotene biosynthetic pathway.

The researchers packaged psy into the plasmid of a disarmed Agrobacterium—the workhorse of plant genetic engineering—together with a root-specific promoter derived from potatoes, a 5´ leader sequence consisting of plant DNA that shuttles the protein into root-bound plastids, and the standard 3´ untranslated region (UTR) from mRNA. Cahoon recalls the first time he saw the successfully engineered cassava root (the part of the plant that’s eaten), in 2007. “It was a good day,” Cahoon says. “[The cassava] was noticeably orange.”

Cassava ß-Carotene is a dietary precursor of vitamin A that is synthesized by the methylerythritol phosphate (MEP) pathway in plastids of some plant cells. Conventional cassava roots lack some of the essential enzymes necessary to produce ß-carotene. The initial step in the pathway is controlled by deoxyxylulose-5-phosphate synthase (DXS), which is added to Cahoon’s cassava via the gene dxs , originally sourced from a different plant species. Additional steps generate the C5 isopentenyl diphosphate (IPP) that is used as the building block for the synthesis of the C20 geranylgeranyl diphosphate (GGDP). Phytoene synthase (PSY), the product of an introduced gene (psy) from a bacterial source, combines two molecules of GGDP to form phytoene, which is converted to ß-carotene via lycopene through a series of desaturation, isomerization, and cyclization reactions. The end result is a noticeably more orangey cassava root.

Meanwhile, Cahoon decided to try inserting the Arabidopsis gene, 1-deoxy-d-xylulose 5-phosphate synthase (dxs), which regulates the isoprenoid pathway, a set of biochemical reactions further upstream from the biosynthetic step in which psy is involved. Inserting dxs, which increases the amount of chemical precursors to beta-carotene, was “like turning up the whole isoprenoid pathway,” Cahoon says. He found that inserting both the psy and dxs genes resulted in a cassava even more orange than the roots with only the psy modification—and with 30 times more beta-carotene than normal roots.
“It’s an informal chain of influence that discourages African farmers from planting any GM crops at all.”

After running more greenhouse trials on plants with both the single and double genetic modifications and choosing the cassava with the most beta-carotene, Cahoon and his team sent tissue samples to Puerto Rico, where scientists propagated clonal offspring. Now, the cassava plants are growing in field trials, which Cahoon recently visited. “They’re looking good,” he says. “For the most part they look like the control plants,” which contain normal levels of beta-carotene.

Eventually, the BioCassava Plus program hopes to move into its second phase—set to commence in 2010 with an additional infusion of funding—in which nutritional modifications to increase iron, zinc, protein, vitamins, and virus resistance will be combined into one cassava plant. “We would actually address all of the deficiencies in cassava in a single cultivar,” says Richard Sayre, a molecular biologist at the Danforth Plant Science Center in St. Louis and director of the BioCassava Plus program. But, as he and Cahoon learned from Golden Rice, getting the science right is just the first step.

There are reasons Cahoon and his colleagues picked Puerto Rico as the site of field tests for the beta-carotene–boosted cassava. Puerto Rico enjoys a tropical climate like much of the core cassava growing areas of Africa but, equally important, the island territory operates under the laws and regulations of the United States, not Africa. “It’s not Africa, but getting in the field in Puerto Rico is a much simpler process than getting through the regulatory processes in Africa,” Cahoon says.

It’s this regulatory tangle facing GM crops in much of the world, including Africa, that largely explains why many transgenic plants that could address widespread nutrient deficiencies are trapped in laboratories instead of growing in soil.

According to Val Giddings, president of Prometheus Agricultural Biotech, most of the restrictions stem from European politics, as influenced by vocal anti-GM groups. Giddings, who helped craft the US Department of Agriculture’s GM crop regulations in the early 1990s as a geneticist at the agency’s Animal and Plant Health Inspection Service (APHIS), says that European countries have effectively exported their restrictive regulations by “making their overseas development programs a slave to their domestic political policies.” In 2004, American officials entreated EU officials to reassure three African nations—Zimbabwe, Zambia and Mozambique—that the hundreds of thousands of tons of GM food aid they had rejected was in fact safe; the EU refused. Add to this the influence that European importers and governments have over food producers in Asia and Africa, and the developing world’s soil is rendered pretty infertile for GM crops. Robert Paarlberg, a Harvard political scientist and author of the book Starving for Science, concurs about the difficulties in getting biotech crops into developing nations. “It’s an informal chain of influence,” he says, “that discourages African farmers from planting any GM crops at all.”

Even in the United States, GM regulations are cumbersome and require a team of people to navigate. Agricultural biotech entrepreneurs, like drug developers, often cite a 10-year time frame to go from initial discovery to saleable product. But compared to the European system, the US regulatory system is manageable. For the beta-carotene–fortified cassava to gain approval from the Department of Agriculture (USDA), for instance, the agency would require data indicating that the introduced genetic construct stably integrated, that the introduced gene does not cause plant disease or produce an infectious agent, and that the cassava was not modified using a gene derived from human or animal pathogens, among other criteria. “It may feel cumbersome to people, but I don’t think [the regulations] are unreasonable,” says Mark Manary, a pediatrician at Washington University in St. Louis who collaborates on the BioCassava Plus program and spends more than half the year working with aid groups in the African nation of Malawi.

However, even if scientists get past the regulatory hurdles associated with any GM foods, there is another practical obstacle that stands in the way of fields full of nutrient-packed cassava or carrots: These foods will cost more than the non-modified versions, and the people who most need them are also the least able to afford them.

In a basement lab at a DuPont research facility, a technician loads bright green soybean tissue samples into a “gene gun,” an unassuming contraption that looks more like a toaster oven than a firearm, and shoots gold nanoparticles coated with DNA molecules into soybean cells at more than 1500 kilometers per hour. The machine makes a muffled pop and the deed is done. DNA will incorporate into the soybean genome and inhibit the activity of fatty acid saturase-2, an enzyme that normally catalyzes the biochemical conversion of oleic to linoleic acid in the soybean plant. Plant molecular biologist Ted Klein stands by, watching. “If we knock out the expression of that enzyme, specifically, in the seed at the right time, then there’s no detrimental impact on the whole plant,” he says.
Cathie Martin's purple tomatoes have 20% more anthocyanins than conventional ones.
Photo by Andrew Davis and Sue Bunnewell

Elsewhere in DuPont’s Wilmington, Del.–based experimental station, giant walk-in coolers feature lines of bright fluorescent bulbs glowing above rows of the modified soybean plants that grew from tissues earlier shot with the gene gun. While they may not address nutrient deficiencies in poverty-stricken corners of the globe, these plants may one day reduce the need to use hydrogenated oils—AKA the dreaded trans fats—in frying, for example. For now, the plants simply stretch to gather as much of the light as possible; eventually, they will produce oil that is more stable in storage and cooking conditions, with 20% less saturated fat and a higher proportion of oleic acid than normal soy oil. The company will screen these soybeans in the grow room looking for the best phenotypes, which develop after several semi-random gene gunshots. DuPont and Pioneer Hi-Bred, the DuPont company that managed the research and development of the technology behind the plants, known as Plenish, hopes to sell “high oleic oil” from the beans to food processing companies, restaurant chains, and other industrial customers around the world as early as the end of this year. With such a market, the company isn’t too concerned about finding customers who can afford the technology.

Tomato Anthocyanins are types of antioxidants, which have been linked to many health benefits. Adding two genes (Del and Ros1) originating from the snapdragon genome to conventional tomatoes, leads to the upregulation of several key enzymes in the pathway, including phenylalanine ammonia lyase (PAL), anthocyanidin synthase (ANS), flavonoid 3-O-glucosyltransferase (3-GT), flavonoid 3-O-glucoside-rhamnosyltransferase (RT), anthocyanin acyltransferase (AAC), flavonoid-5-glucosyltransferase (5-GT), and glutathione S-transferase (GST) and putative anthocyanin transporter (PAT), which may be involved in transport of anthocyanins into the vacuoles of cells within the tomato's flesh. The end result is a tomato with a threefold increase in antioxidants and very empurpled flesh.

The oil has already been approved by Mexican and Canadian regulatory agencies. “Now we’re just waiting for the USDA,” says Susan Knowlton, a DuPont research manager.

Other scientists are also trying to tweak the nutritional content of common foods. Kendal Hirschi, a Baylor University pediatrician and geneticist, has genetically engineered a carrot that contains twice the calcium of normal carrots by upping the expression of a plant calcium transporter (sCAX1) in the roots with the addition of an Arabidopsis gene construct. He’s even performed a pilot nutritional study, which was funded by the National Institutes of Health, where subjects absorbed about 40% more calcium from his carrots than they did from normal carrots.2 Feeding studies are essential if nutritionally enhanced GM foods are going to have a real-world impact, Hirschi says. “None of these improvements are any good until we actually show they’re good in the food supply.”

In order to ensure that the technology has a buyer, that could perhaps compensate for the expense of distributing it free or below cost to the developing world, Hirschi is trying to attract attention from large food company General Mills, which has expressed some interest in his carrots as a way to make thicker canned soups. (Calcium chloride is often added to foods as a thickener.)

Cathie Martin, a geneticist at the John Innes Centre in Norwich, UK, has developed a tomato variety that may prove useful to consumers worldwide, not just the malnourished. Martin’s deep purple tomato has 20% higher levels of anthocyanins, antioxidants that may guard the body against chronic diseases and cancer. She and colleagues recently showed that mice consuming a diet that includes her GM tomatoes, whose boosted antioxidant profile is thanks to two transcription factors from snapdragons, lived an average of 30% longer than mice that consumed regular tomatoes.3 Western countries—where people tend not to get the recommended 5 fruits and vegetables per day, and the giant food companies that operate therein—can play a role in moving these types of GM foods closer to a widespread reality, Martin says. “You’ve got to get the food companies interested in sowing better foods,” she says. “If you can improve tomatoes, then you can get the good things in fruit and vegetables into something that people actually eat.”

“We know how this story ends,” says Val Giddings—nutritionally fortified, GM foods will get into the global marketplace and the mouths of the people who need them. “You can’t stop the tide. Biotech will, in time, become the new conventional agriculture. The question is how long will it be until that happens, and what, if anything, can we do to accelerate the process.”

There are hints now emerging that bear out Giddings’ prediction. Since first introducing the world to Golden Rice in 2000, Beyer’s collaborators have developed new versions of the beta-carotene–enhanced grain. Golden Rice 2, which Beyer says will be available on the market in the Philippines and in Bangladesh within the next 2 or 3 years, contains 30–35 micrograms of beta-carotene/gram—more than 30 times more beta-carotene than the original kernel introduced in 2000.4 Beyer and his colleagues accomplished this massive increase by tinkering with the promoter sequences used in the genetic modification, by changing the source of one of the gene inserts from daffodils to maize (which boosts beta-carotene production), and other subtle tweaks to the science behind Golden Rice. This new version recently completed feeding trials5 and is now growing in experimental plots in the Philippines and Bangladesh.

Golden Rice Wild-type white rice produces geranylgeranyl-diphosphate (GGPP), a precursor of ß-carotene. However, the grain endosperm lacks phytoene synthase, which catalyzes the conversion of GGPP to phytoene. Golden Rice 1 was engineered to express daffodil phytoene synthase, while Golden Rice 2 uses a more efficient maize version of the gene. Zeta-carotene desaturase, an enzyme expressed by a gene from the soil bacterium Erwinia uredovora, further increases ß-carotene levels in the grain.

But the research was relatively easy—to create a GM product that regulators and citizens would accept, Beyer needed help. Funding came from philanthropic organizations, such as the Bill and Melinda Gates Foundation, the Rockefeller Foundation, and government aid agencies, such as the United States Agency for International Development. A private-public partnership between Golden Rice’s inventors and the agrichemicals company Syngenta, along with several collaborations with research institutions throughout Asia, made the imminent market introduction of Golden Rice possible, Beyer says. The project is now conducting the social marketing research and local rice variety back-crosses, which will blend the beta-carotene trait into locally popular rice varieties—both necessary to successfully and safely introduce the crop and get farmers to grow the plants.

The BioCassava Plus program has also recently seen significant progress in its goal to introduce biofortified foods into the developing world. Director Richard Sayre says that the program’s pro-vitamin A cassava plants have been approved for field trials in Nigeria, the world’s number one consumer of the food. In July, the country planted between 4000 and 8000 m2 with Cahoon’s two-gene GM cassava, the first GM product Nigeria has field tested. “We are quite proud of that,” Sayre says. To advance the BioCassava Plus program to the next stage, Sayre says that more donor money will be needed. He says that the program is “planning on approaching other donors,” but declined to name them.

Navigating through Nigeria’s regulatory approval process was no small task, Sayre says, for which the BioCassava Plus program enlisted the help of Nigeria’s National Root Crop Research Institute (NRCRI) and a Nigerian product developer who was a former member of the county’s National Biosafety Committee. “We think that was an important part of our strategy,” Sayre says, “because it meant that the government was buying into the process.” The Nigerian regulations, for example, required experimenters to dig a fence around the experimental plots a meter deep into the soil to prevent burrowing animals from carrying off bits of the GM cassava. The Nigerian regulations were “redundancies upon redundancies of protection,” according to Sayre.
“You can’t stop the tide. Biotech will, in time, become the new conventional agriculture.”

To ensure the cassava gets where it needs to go, the project will again call upon the infrastructure and local knowledge of national agriculture research institutions such as the NRCRI and nongovernmental organizations to distribute the cassava plants to poor farmers for free or for a nominal fee. The BioCassava Plus project will utilize the traditional dissemination scheme—where farmers share cuttings of their successful plants with friends and neighbors—to further disseminate their enhanced cassava. (The Gates Foundation, in fact, requires that the technology come with royalty-free humanitarian license.) Poor farmers can get and share cuttings for free, while those who make more than $10,000 per year must pay a royalty fee to companies like Monsanto that donated enabling technologies (patented Agrobacterium transformation systems, and gene promotors, for example) to the project. Sayre also says that a “very critical” part of the BioCassava project is to eventually transfer research and production capabilities and responsibilities to African labs, scientists, and countries. “I put myself out of business in many ways,” he says.
Golden Rice 2 contains more than 30% more beta-carotene than the first Golden Rice.
Photo courtesy of Golden Rice Humanitarian Board

Other GM advocates say they hope cassava is not the only biofortified food to be planted in Nigeria. “What I’d like to see is hundreds of millions of very poor people improving their nutritional status and improving their health status,” says Lawrence Kent, senior program officer of agricultural development at the Bill and Melinda Gates Foundation, which funds genetic research in biofortification, but also donates money to efforts aimed at conventional fortification, supplementation, and dietary diversification. “We’re hoping some initial successes are going to trigger additional interest, especially from national governments. If we can help get more nutrients into these staple foods, we really can help millions of people improve their lives.

References
1. X. Ye et al., “Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm,” Science, 287:303–5, 2000.
2. J. Morris et al., “Nutritional impact of elevated calcium transport activity in carrots,” PNAS, 105:1431–35, 2008.
3. E. Butelli et al., “Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors,” Nat Biotech, 26:1301–8, 2008.
4. J.A. Paine et al., “Improving the nutritional value of Golden Rice through increased pro-vitamin A content,” Nat Biotech, 23:482–87, 2005.
5. G. Tang et al., “Golden Rice is an effective source of vitamin A,” Am J Clin Nutr, 89:1776–83, 2009.

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Golden Rice to hit market by 2011

- Food and Beverage News (India), Sept. 1, 2009 http://www.fnbnews.com

A genetically modified variety of rice called the Golden Rice will hit the market by 2011. This rice is developed to produce a carotenoid called beta carotene which gives the rice an orange-yellow hue, and hence its name. Moreover, the beta carotene becomes vitamin A when processed by the body, according to a report from Manila, Philippines. As per WHO statistics, four out of 10 children aged between six months and five years, and three out of 10 school children show symptoms of vitamin A deficiency. Similarly, 50% lactating and pregnant women also suffer from problems associated with vitamin A deficiency. Since rice is a staple in many Indian states, vitamin A fortified Golden Rice will be a boon to children and nursing mothers. As per data available in the Philippines, daily consumption of three cups of cooked Golden Rice can meet the vitamin A requirement of a person. Moreover Golden Rice also has the nutritional properties that can arrest avoidable blindness in children.

Research on this rice variety has been going on for more than a decade. The Golden Rice technology is based on a simple principle. Rice plants accumulate beta carotene in their leaves but not in the grain. By the addition of two genes -- phytoene synthase and phytoene desaturase - using modern technology, the beta carotene gets accumulated in the endosperm, which is the edible part of the grain. The technology involved in developing Golden Rice is free because its inventors have released all intellectual property rights to the public through the Golden Rice Humanitarian Board.

Golden Rice is expected to be released in the Philippines in 2011. Markets in India and Vietnam too are expected to get their version of Golden Rice during the same period. The first Golden Rice was developed by Dr Ingo Potrykus and Dr Peter Beyer in 2000. Later, the duo teamed up with Syngenta, which produced Golden Rice with higher levels of beta carotene. Syngenta donated these materials to the Golden Rice Humanitarian Board, which oversees development of Golden Rice in rice-producing countries, including India.

Golden Rice-1 was developed in 2003 and Golden Rice-2 in 2005. At present, the Philippine Rice Research Institute, popularly known as PhilRice, is developing a new Golden Rice variety that will be resistant to pests like tungro and bacterial blight.

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GM Crops: Battlefield

- Emily Waltz, Nature 461, 27-32 (2009) . Full text at
http://www.nature.com/news/2009/090902/full/461027a.html

Papers suggesting that biotech crops might harm the environment attract a hail of abuse from other scientists. Emily Waltz asks if the critics fight fai

Emma Rosi-Marshall's trouble started on 9 October 2007, the day her paper was published in Proceedings of the National Academy of Sciences (PNAS). Rosi-Marshall, a stream ecologist at Loyola University Chicago in Illinois, had spent much of the previous two years studying 12 streams in northern Indiana, where rows of maize (corn), most of it genetically engineered to express insecticidal toxins from the bacterium Bacillus thuringiensis (Bt), stretch to the horizon in every direction.

Working with colleagues including her former adviser Jennifer Tank at the University of Notre Dame, Indiana, Rosi-Marshall had found that the streams also contain Bt maize, in the form of leaves, stalks, cobs and pollen. In laboratory studies, the researchers saw that caddis-fly larvae — herbivorous stream insects in the order trichoptera — fed only on Bt maize debris grew half as fast as those that ate debris from conventional maize. And caddis flies fed high concentrations of Bt maize pollen died at more than twice the rate of caddis flies fed non-_Bt pollen. The transgenic maize "may have negative effects on the biota of streams in agricultural areas" the group wrote in its paper, stating in the abstract that "widespread planting of Bt _ crops has unexpected ecosystem-scale consequences"1.

The backlash started almost immediately. Within two weeks, researchers with vehement objections to the experimental design and conclusions had written to the authors, PNAS and the US National Science Foundation (NSF), Rosi-Marshall's funder. By the end of the month, complaints about the paper had rippled through the research community. By the time Rosi-Marshall attended a National Academy of Sciences (NAS) meeting on genetically modified organisms (GMOs) and wildlife on 5 November 2007, "She looked hammered", says Brian Federici, an insect pathologist at the University of California, Riverside, one of those who commented on her work. "I felt really sorry for her. I don't think she realized what she was getting into."

No one gets into research on genetically modified (GM) crops looking for a quiet life. Those who develop such crops face the wrath of anti-biotech activists who vandalize field trials and send hate mail. But those who, like Rosi-Marshall and her colleagues, suggest that biotech crops might have harmful environmental effects are learning to expect attacks of a different kind. These strikes are launched from within the scientific community and can sometimes be emotional and personal; heated rhetoric that dismisses papers and can even, as in Rosi-Marshall's case, accuse scientists of misconduct. "The response we got — it went through your jugular," says Rosi-Marshall.

Problem papers
Behind the attacks are scientists who are determined to prevent papers they deem to have scientific flaws from influencing policy-makers. When a paper comes out in which they see problems, they react quickly, criticize the work in public forums, write rebuttal letters, and send them to policy-makers, funding agencies and journal editors. When it comes to topical science that can have an impact on public opinion, "bad science deserves more criticism that your typical peer-reviewed paper", Federici says.

But some scientists say that this activity may be going beyond what is acceptable in scientific discussions, trampling important research questions and stifling debate. "It makes public discussion very difficult," says David Schubert, a cell biologist at the Salk Institute in La Jolla, California, who found himself at the sharp end of an attack after publishing a commentary on GM food2 (see 'Seeds of discontent'). "People who look into safety issues and pollination and contamination issues get seriously harassed."
Protesters can brandish science suggesting that genetically modified crops are harmful.P. PAVANI/AFP/GETTY

To see the effect that biotech crop research can have on policy — and why some researchers feel that they need to weigh in against such studies as quickly and forcefully as possible — it is instructive to look back to a study3 published in Nature in 1999. In it, John Losey, an entomologist at Cornell University in Ithaca, New York, and his colleagues reported that nearly half of the monarch butterfly caterpillars eating leaves dusted with Bt maize pollen died after four days, compared with none exposed to untransformed pollen. The media and the anti-GMO community erupted. "Gene Spliced Corn Imperils Butterflies" headlined the 20 May 1999 San Francisco Chronicle. Greenpeace activists demonstrated in front of the US Capitol dressed as monarch butterflies, collapsing from 'killer' GM maize.

In response, the US Environmental Protection Agency (EPA) told seed companies to submit data about the toxicity of Bt maize pollen in monarch butterflies or lose the right to sell the maize. Scientists dived into the research, using industry and government funding. The effort produced six PNAS papers in 2001 that concluded that the most common types of Bt maize pollen are not toxic to monarch larvae in concentrations the insects would encounter in the fields4. (Losey had used higher concentrations in his lab studies.) "The Losey paper resulted in a lot of good work and brought to a close that particular question," says Alison Power, who studies ecology and evolutionary biology at Cornell University. Yet some scientists were dismayed that a single paper with preliminary data gave so much ammunition to anti-GMO activists and caused an expensive diversion of resources to calm the scare. They did not want it to happen again.

The caddis-fly study was Tank and Rosi-Marshall's debut in GM research. The idea stemmed from a 2002 talk that Tank gave at Michigan State University in East Lansing about nitrogen dynamics in streams. A researcher in the audience asked whether organic debris from fields of transgenic maize drains into streams, and whether it has any effect on stream life. "We've never thought about that," Tank told the questioner. And once the paper was complete, Tank, Rosi-Marshall and their collaborators had little idea of the storm it was about to kick up. "I thought the response would be 'So what? We're going to lose a few trichopterans'," says co-author Todd Royer, an assistant professor at Indiana University in Bloomington.

On a Friday after the paper was published, Federici and plant biotechnologist Alan McHughen, also at the University of California, Riverside, met at a campus bar for a beer after work. "[McHughen] was really annoyed," says Federici. "I don't think there's been another case where I've seen him so really ticked off." Federici says he too was annoyed — Rosi-Marshall's study was "bad science", he says, and they feared that activists would use it to forward an anti-GMO agenda. McHughen and Federici wanted to neutralize any effects that Rosi-Marshall's paper might have on policy.

The two discussed the key points of a rebuttal letter. McHughen wrote the critique and "circulated it around to people who might be sympathetic", says Federici. The letter listed six grievances with the "sloppy experimental design", and said the publication of the paper had "seriously jeopardized the credibility of PNAS". "How many busy scientists and how much scarce money will we need to divert to calm this new scare?" the researchers wrote. McHughen got ten other scientists' signatures, including Federici's. On 22 October, they sent the letter to the journal and to the NSF. Days later, Klaus Ammann, a retired botanist and professor emeritus at the University of Bern in Switzerland who had signed the McHughen letter, posted it on an online discussion forum5.

Critical mass
Wayne Parrott, a crop geneticist at the University of Georgia in Athens, also began working on a rebuttal to Rosi-Marshall's paper as soon as he saw it. He said recently that in his opinion: "The work is so bad that an undergrad would have done a better job. I'm convinced the authors knew it had flaws." He e-mailed the authors, the NSF and PNAS two bulleted lists of flaws that he said invalidated the paper. He wrote: "It is risky to extrapolate from lab results to field results, particularly when key factors were not monitored, measured or controlled appropriately." In January 2008, PNAS published a slimmed-down version of this letter6 and the one from McHughen7.

Tank and Rosi-Marshall were dismayed by Parrott's e-mail. A few days after receiving it, Tank called James Raich, her contact at the NSF, to talk it over. "I told her to ignore it," says Raich, an ecosystem ecologist at Iowa State University in Ames who worked for the NSF for two years reviewing grant proposals. He told her that letters like these were unusual. But the critiques kept on coming. On 30 November, Monsanto, a maker of Bt maize based in St Louis, Missouri, sent the EPA a six-page critical response8 to the paper, and posted it online. Eric Sachs, director of global scientific affairs at Monsanto, says that regulators ask seed companies to notify them of papers that relate to crop safety, so Monsanto often includes with its notification evaluations of these papers.

Four other signatories of the McHughen letter went on to publish scathing opinion articles over the next few months. In a March 2008 article9 criticizing four papers on biotech crops, Ammann joined forces with Henry Miller, a research fellow at the Hoover Institution in Stanford, California, to ask "Is biotechnology a victim of anti-science bias in scientific journals?". They called Rosi-Marshall's conclusions "dubious", and said their use of evidence "arguably amounts to investigator misconduct". And in a July 2008 commentary in Current Science10, Shanthu Shantharam, a visiting research scholar at Princeton University in New Jersey said Rosi-Marshall's "offending" paper "carried a wrong message to farmers and environmentalists", and that anti-biotech crop activists would use the paper to "hamper the progress of science".

Rosi-Marshall took the hits hard. "I experienced it in person and in writing," she says. "These are not the kind of tactics we're used to in science." She was a few years out from her PhD, she did not have tenure at Loyola and her first paper in a prominent journal was getting trashed, along with her reputation. "She's young and was getting picked on," says Michelle Marvier, a biologist at Santa Clara University in California who attended the NAS November 2007 meeting.

It was at least some comfort to Rosi-Marshall and Tank that e-mails and phone calls of encouragement came pouring in from other scientists. Some of their supporters had observed similar attacks on other biotech crop papers. "The most reassuring thing we learned was that it had happened before and by the exact same people," says Tank.

What was it about Rosi-Marshall's paper that prompted such a strong reaction? The wording of the abstract — "widespread planting of Bt crops has unexpected ecosystem-scale consequences" — was a particular point of contention. Her critics say that the data do not support such a definitive conclusion. "They absolutely went too far," says Randy Schekman, editor-in-chief of PNAS. Of the half-a-dozen letters received by the journal, most of them protested at this wording, he says. "Why this would have escaped the attention of the referees beats me."

The authors agree that the wording was unfortunate and in retrospect say that the sentence should have articulated the potential for ecosystem-scale consequences within streams, rather than suggesting that such consequences were observed. "This was an oversight," says Rosi-Marshall. "But we did not expect that this sentence would, in light of all of the other statements in our paper, elicit the response it did. We thought the paper would be taken as a whole."

The study's methods also came under fire. It is unclear, for example, whether it was the Bt toxin itself affecting the caddis flies, or some other difference between Bt and non- Bt plants. To test this possibility, critics say the caddis flies should have been fed isogenic lines: strains of maize that are genetically identical except for Bt genes. The authors say they chose not to use such lines because their nutritional quality would have differed — Bt maize has higher concentrations of lignin than non- Bt maize, and so is less nutritious. So the authors matched the Bt samples with non- Bt samples that had similar levels of lignin and other nutrients. "To do otherwise would have resulted in a confounded experiment. Pairing the treatment on the basis of isolines might be standard for agronomic studies, but was inappropriate for an ecological feeding study," the authors told Nature in an e-mail. Rosi-Marshall and her colleagues made this point and other responses to their critics in a correspondence11 published online in PNAS the week after McHughen's and Parrott's critiques.

It is also unclear how much Bt toxin the caddis flies ate. The authors let the insects eat as much as they wanted, as they would in the wild. Critics argue that the authors should have fed the insects known amounts of the toxin in a method called a dose-response study that is routine in toxicity assessments. "The Rosi-Marshall et al. paper would have benefited from additional toxicological data," says Doug Gurian-Sherman, a senior scientist at the Union of Concerned Scientists in Cambridge, Massachusetts, and a former reviewer for the EPA. But the method the authors used "is a widely accepted method, and is generally adequate for a preliminary study of possible toxicity", he says.

Omitted study
The paper was also accused of omitting contrary findings. In June 2007, four months before Rosi-Marshall's PNAS paper was published, Jillian Pokelsek, a master's student at Loyola University Chicago working with Rosi-Marshall, presented results from a preliminary field experiment at the annual meeting of the North American Benthological Society in Columbia, South Carolina. The work showed that Bt maize pollen did not influence the growth or mortality of filter-feeding caddis flies. The society posted an abstract12 of the presentation on its website attributing the work to Pokelsek, Rosi-Marshall, Tank, Royer and four other scientists who also authored the PNAS paper. It was not mentioning this study that prompted Miller and Ammann's accusation of misconduct9.

The authors defend the omission on the grounds that the data in the meeting presentation were not published or peer-reviewed, and were less reliable than those in the PNAS paper. "Field experiments are inherently difficult to control and have lower statistical power to detect significant differences compared with controlled laboratory experiments, thus we included the more controlled and statistically rigorous lab experiments in our paper," Tank and Rosi-Marshall told Nature. Also, the caddis flies in the student presentation belonged to a different family, with different feeding mechanisms to those in the PNAS study. Miller's response: "I don't want to split hairs," he says. "If you don't do appropriate controls or if you draw conclusions that are erroneous, I think that's misconduct." But Ammann says he has a "bad feeling" about the accusation. "Maybe we should have been more careful with the wording."

Scientists who were not involved in the debate over Rosi-Marshall's paper say the results were preliminary and left some questions unanswered, but that overall the data are valuable. "The science is fine as far as I'm concerned," says Arthur Benke, an aquatic ecologist at the University of Alabama in Tuscaloosa, who called the strong language in some of the criticisms "inappropriate".

What drives the critics? Financial or professional ties to the biotech industry don't seem to be the impetus. Such ties do exist — like many people researching biotech crops, some have received research grants from industry or have other interactions with it — but in interviews they say that these are not the major driving force. Rather, many of them feel strongly that transgenic crops are safe and beneficial to the environment and society, and that the image and regulation of these crops has been too harsh. Many of the critics have been studying biotech crops since they were developed commercially in the late 1980s, and some were involved with the first regulatory approvals. They have specific ideas about how the risks of these crops should be scientifically assessed. And they worry that papers that fall short of high standards will give anti-GMO activists ammunition to influence policy, just as the monarch-butterfly study did. "When bad science is used to justify bad public policies, we all lose," says McHughen, who says he is on a "campaign to make academic scientists a little less politically naive and a bit more careful in their scientific work". Miller adds that "agricultural biotech has been so horrendously, unscientifically regulated and so over-regulated and so inhibited over the past 30 years that to have these pseudo-controversies stirred up unnecessarily does a disservice to everyone and everything".

Ammann points to the example of golden rice, a variety engineered in the late 1990s to contain more vitamin A. Regulations have delayed the rice's development, he says, although more than 250,000 children a year go blind from vitamin-A deficiency. "We have to get emotional," says Ammann. "I can't agree with the cool scientists' perspective — only dealing with the facts. We live in the real world." In 2006, Ammann formed a rebuttal team called ASK-FORCE to challenge reports about biosafety of GM crops. On one online site, Ammann criticizes 20 reports — none of them positive toward biotech crops — that he considers biased or bad science. In July, he was revising a critique of a paper that appeared in The Lancet ten years ago. "I'm working nearly day and night on these things," says Ammann.

The emotional and sometimes harsh quality of some of the attacks strikes some scientists as strange and unlike the constructive criticism to which they are accustomed. Benke points out that none of the criticisms on the caddis-fly paper, for example, called for further study on the insects. "What papers like this do is alert us to possible reasons to look into this more carefully," he says. "No one mentioned this." To try to dismiss the research out of hand ignores how science is supposed to work, adds Power — you make a hypothesis, test it, refine it, test it and refine it again. "You keep doing that until you have an answer that is as close as you're going to get," she says. "I don't understand the resistance to that notion."

Arbiters of the truth
Some scientists say they are galled by the certainty with which some of the critics state their opinion. "Part of what exasperates me is that they have declared themselves to be the experts in this field, and forcefully present themselves as the ultimate arbiters of truth," says an editor for the Entomological Society of America who asked to remain anonymous. "I personally am in favour of GMOs in general, and think that they are very beneficial for the environment. But I do have problems with the tactics of the large block of scientists who denigrate research by other legitimate scientists in a knee-jerk, partisan, emotional way that is not helpful in advancing knowledge and is outside the ideals of scientific inquiry."

The critics respond that they are simply pointing out flaws in research, and that this is an important part of the scientific process. "It is neither fair nor accurate to equate pointing out serious deficiencies with experimental design and data interpretation as 'denigration'," Parrott says. "For science to maintain its integrity and move forward, it is critical to assert the right of scientists to question each other's work." McHughen says that he doesn't condone ad hominem attacks. "They are invariably unproductive," he says, and points out these tactics are often used against scientists who don't oppose GM crops.

Federici says he finds it inappropriate to call the reactions 'knee-jerk' ones. "Losey and colleagues, and Rosi-Marshall and colleagues at the time of their studies were newcomers to the field. Most of the people who found their studies flawed and protested had extensive experience with Bacillus thuringiensis." He also points out that the critics varied in how strongly they responded to the Rosi-Marshall paper, saying "I don't consider writing a letter to the editor a harsh response."

Ignacio Chapela, a microbial ecologist at the University of California, Berkeley, says that the attacks may be deterring young scientists from pursuing careers in biotech crop research. "I have a very long experience now with young people coming to me to say that they are not going into this field precisely because they are discouraged by what they see," he says. Chapela faced criticism from pro-GMO scientists after publishing a 2001 paper in Nature, in which he reported that native maize varieties in Mexico had been contaminated with transgenic genes13. Following the criticism, Nature decided that "the evidence available is not sufficient to justify the publication of the original paper".

At its worst, the behaviour could make for a downward spiral of GM research as a whole, says Don Huber, a emeritus professor of plant pathology at Purdue University in West Lafayette, Indiana. "When scientists become afraid to even ask the questions … that's a serious impediment to our progress," he says. Miller says: "I don't see how criticism of flawed science that verges on misconduct should discourage anybody." Researchers could be invigorated by entering a field with such lively debate. "For some people it might be exciting because you're doing science that is relevant to society," says Power.

Pervasive spread
Rosi-Marshall's caddis-fly paper did find its way into the anti-GMO rhetoric, although on nowhere near the scale that the monarch butterfly paper did. For example, the London-based Institute of Science in Society, a not-for-profit organization involved in the GM debate, on 30 October 2007 posted its summary of the paper, saying that: "calling a halt to planting Bt corn next to streams … would be in keeping with the evidence [the authors] have provided". Greenpeace included the paper in an April 2008 briefing on Bt maize, citing it as evidence of environmental risk.

The impact went further than that. On 9 January 2008, three months after Rosi-Marshall's paper was published, France's watchdog on GM foods ruled that one of Monsanto's types of Bt maize, known as MON810, may have an impact on wildlife. The evidence it cited included Rosi-Marshall's paper. Two days later, the French government announced a ban on cultivating the maize. "[The paper] got to every agency and non-governmental organization that doesn't like the technology and gave them a flag to wave," says Parrott. Not that he considers the effort wasted: "I have no doubt the impact on policy-makers would have been much worse had it not been countered."

Nearly two years since the paper was published, the critics' comments are still pointed. "It was just an idiotic experiment," Miller said this July. But Rosi-Marshall and her co-authors stand behind their paper. "We believe our study was scientifically sound," they wrote in an e-mail, "although many questions on the topic remain to be answered. The repeated, and apparently orchestrated, ad hominem and unfounded attacks by a group of genetic engineering proponents has done little to advance our understanding of the potential ecological impacts of transgenic corn."

And Rosi-Marshall's career seems to have survived the furore. In May 2009 she secured tenure at Loyola University Chicago, and in August she moved to the Cary Institute of Ecosystem Studies in Millbrook, New York. There she will study human-dominated ecosystems and will continue to investigate the influence of maize varieties on stream ecosystems. Since the caddis-fly paper, she has co-authored another study on transgenic crops showing that Bt maize debris decomposes in streams at a faster rate than conventional maize14. She says more data produced with the NSF grant are on the way and that the attacks won't deter her from her studies.

"It toughened me up a lot," she says. "I'm not going to be intimidated."