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Food firms test fry Pioneer’s trans fat–free in brief soybean oil Anti-CD20 patent battle ends On June 1, a four-year dispute over a European The US Department of Agriculture (USDA) market has gone from 76% in 2005 to 64% patent for anti-CD20 drugs to treat rheumatoid has approved for environmental release one of today, according to the US Census Bureau. arthritis came to an end, with Seattle-based the first biotech crops aimed at the food indus- “We hope to recapture that space [for soy- Trubion winning the dispute. This result frees up the space for anyone with a CD20 program, says try. The new crop, a genetically modified soy- beans],” says Pioneer’s Russ Sanders, director Jeff Pepe, associate general counsel at Trubion. bean with an altered fatty acid profile, yields oil of enhanced oils. Multiple oppositions had been filed against the that is more stable at high frying temperatures Pioneer’s new soybean oil has an oleic fatty patent (European Patent 1176981) held jointly and has a longer shelf life than commodity soy- acid content of >75%, a property that gives it by of S. San Francisco, California, bean oil. It was developed by Pioneer Hi-Bred frying and shelf stability comparable to that and Idec of Cambridge, Massachusetts. Trubion was joined by MedImmune, GenMab, in Johnston, Iowa, a Dupont company. The of palm, high oleic acid canola and hydroge- Centocor, the Glaxo Group and Merck Serono, all company received marketing approval for the nated soybean oils. It also contains 20% less pursuing anti-CD-20 programs at one time. In biotech soybean in June and aims to commer- saturated fat than commodity soybean oil. 2008, the Opposition Division of the European cialize it by 2012. St. Louis–based Monsanto Pioneer dubbed the crop “Plenish high-oleic Patent Office ruled that, as filed, the patent did is following close behind, with two soybean soybeans.” Overproduction of oleic acid and not meet the necessary requirements, favoring products with modified oil profiles in its pipe- decreased levels of linoleic and linolenic acids Trubion. Genentech and Biogen appealed in 2009. Finally, at an oral hearing this June, line. in Plenish arise from the original ruling was upheld, and no further The new soybean transgenic expression appeals will be allowed. Ironically, around the traits may help the of a fragment of the time of the hearing, New York–based , biotech industry soybean microsomal which acquired Trubion’s CD20 programs when deliver on a two- omega-6 desatu- it bought in 2009, announced they would drop Trubion’s lead anti-CD20 compound (TRU- decade-long promise: rase gene (FAD2-1) 015) though retaining the biotech’s second to develop crops with under the control generation anti-CD20 also improved nutritional of soybean Kunitz in rheumatoid arthritis. For Genentech/Roche value. Until now, trypsin inhibitor “the decision does not impact our expectations most commercialized gene promoter, which with respect to protection against Rituxan John Lee/i S tockphoto John biotech crops have silences endogenous [rituximab, anti-CD20 chimeric monoclonal antibody],” says company spokesperson been engineered with The success of Pioneer’s recently approved soy omega-6 desatu- bean, which has been engineered to cut down on Rubin Snyder. Laura DeFrancesco such traits as pest trans fats, will depend on how well it is received rase. The transgenic resistance and herbi- by the food industry. soybean also carries cide tolerance—traits the S-adenosyl-l- EU states free to ban GM crops that mostly benefit methionine syn- In July, the European Commission (EC) farmers rather than the food industry or con- thetase as a marker to enable initial selection officially proposed to give member states the freedom to veto cultivation of genetically sumers. “Heat stability and longer shelf life: in the laboratory by acetolactate synthase modified (GM) crops without having to these are the things that can light up the food (ALS)-inhibiting herbicide. back their decision with scientific evidence © 2010 Nature America, Inc. All rights reserved. All rights Inc. America, Nature © 2010 industry, not reduced pesticides,” says Tom The success of the Plenish soybean will on new risks. The reform’s goal is to hand Hoban, a professor of food science at North depend on how well it is received by the food back responsibility to individual states and Carolina State University in Raleigh. industry. Pioneer has already set up testing speed up pending authorizations. Anti-GM Pioneer is marketing its new soybean oil as agreements with a dozen undisclosed food countries can now choose to opt out whereas biotech-friendly countries can cultivate new an alternative to partially hydrogenated veg- companies, says Sanders. The companies will GM varieties. However, there is no guarantee etable oils. For decades, food producers have run consumer taste tests, frying tests and shelf it will work. “We are not against freedom relied on partially hydrogenated soybean oil life tests—just about anything a food company for member states, the problem is how because it retains its flavor at high cooking would normally do with a new ingredient. the principle is articulated,” says Carel du temperatures and for extended periods on the Food companies can already choose from an Marchie Sarvaas, director for agricultural biotech at EuropaBio. The proposal stands on grocery store shelf. But the process of partial array of oils with modified fatty acid contents two legs: an amendment to directive 2001/18 hydrogenation produces trans fatty acids, or developed with conventional breeding. “The that must gain the approval of the council trans fats, which are known to increase ‘bad’ hard reality will be how producers of liquid of ministers and the European Parliament, low-density lipoprotein (LDL) cholesterol and vegetable oils compete,” says Terry Etherton, and an EC recommendation on coexistence, increase risk of coronary heart disease. professor of animal nutrition at Penn State in already effective. The first legalizes national In 2006, the US Food and Drug University Park, Pennsylvania. or local bans on growing, the second one achieves the same result by conceding that Administration began requiring food manu- Food industry representatives say they wel- countries wanting to keep ‘contamination’ facturers to label food with trans fats, and come the new oil option, but see it as a “trial levels well below the labeling threshold can measures to alert the public of the health risks situation,” says Jeffrey Barach, vice president enforce wide isolation distances between of trans fats ensued. Food producers turned of science policy at Grocery Manufacturers GM and conventional or organic fields. “It’s to alternatives, such as palm oil and certain Association in Washington, DC .“Each com- a Pandora’s box. We are concerned it will create legal uncertainty and unpredictability kinds of canola oil, that have more stable fry- pany has to try it out and do some experimen- for farmers and operators,” says du Marchie ing and shelf life characteristics than those tal work,” he says. Sarvaas. The reform doesn’t target imports of of unhydrogenated soybean oil. As a result, Although Pioneer received the full go-ahead GM material for food or feed, whose approvals soybean oil’s share of the edible fats and oils from regulators, the company doesn’t plan to are also stalled. Anna Meldolesi

nature biotechnology volume 28 number 8 AUGUST 2010 769 NEWS

in brief Table 1 USDA-approved soybeans modified for improved trans fat content Product Company Description GM alfalfa—who wins? DP-305423 Pioneer Hi-Bred High oleic acid soybean produced by inserting extra copies of a Both sides are claiming victory following the International portion of the gene encoding omega-6 desaturase, gm-fad2-1, Supreme Court’s verdict issued June 21 in resulting in silencing of the endogenous omega-6 desaturase Monsanto v. Geerston Seed Farms over the gene (FAD2-1). future sale of Roundup Ready (RR) alfalfa DD-026005-3 DuPont High oleic acid soybean produced by inserting a second copy of seeds. The Supreme Court repealed a lower a portion of the gene encoding omega-6 desaturase, gm-fad2-1, court injunction issued in 2007 banning the resulting in silencing of the endogenous omega-6 desaturase biotech seeds nationwide (Nat. Biotechnol. 28, gene (FAD2-1). 184, 2010). Monsanto’s business lead for the OT96-15 Agriculture & Agri-Food Low linolenic acid soybean produced through traditional cross- crop, Steve Welker, says the St. Louis–based Canada breeding to incorporate the trait from a naturally occurring fan1 company has plenty of RR alfalfa seeds gene mutant that was selected for low linolenic acid. “ready to deliver,” although their release is Source: AGBIOS subject to a pending environmental impact statement (EIS) by the US Department of Agriculture (USDA). “Our goal is to have commercialize Plenish soybeans until the first nutrition and the other with enhanced tex- everything in place for growers to plant in fall quarter of 2012, after food players have had ture and functionality, called high stearic 2010,” Welker adds. Not so fast, says lawsuit opponent Andrew Kimbrell of the Center for time to determine what food applications, if acid soybeans. Monsanto has submitted to Food Safety in Washington. He points out any, they want to pursue with Plenish soy- the USDA petitions for deregulation of both that the Supreme Court “just took away the beans. “We’re being fairly conservative in our products. Still in the discovery phase, Dow injunction, and USDA still has to comply with commercialization schedule,” Sanders says. AgroSciences in Indianapolis, Indiana is NEPA [the National Environmental Policy The time to market also depends on developing omega-9 canola and sunflower Act] and complete an EIS” before the crop Pioneer’s ability to secure regulatory approval oils. With one nutritionally altered crop can be deregulated. Although USDA appears poised to complete its EIS and fully deregulate in key global markets, such as Europe, Japan, approved and a handful in the pipeline, RR alfalfa, the Center for Food Safety could China, Taiwan and South Korea, Sanders says. the public may finally get what it has been renew its challenge of USDA’s decision. The soybean is already approved in Canada promised for two decades. But whether This lingering uncertainty has agitated many and Mexico. high oleic acid soybeans directly benefit members of Congress. Seven senators and Global regulatory hurdles hampered consumers enough to boost public opinion 49 representatives have asked agriculture secretary Tom Vilsack to retain regulated status Dupont’s earlier development of a different of biotech crops is doubtful, say agriculture for RR alfalfa, whereas two other senators have high oleic acid soybean (Table 1). In 1997, the experts. “Companies already have methods urged Vilsack to “mount vigorous defenses USDA approved, or deregulated, DD-026005-3 of removing trans fats” from food, says Jane against lawsuits that seek to upend science- —a Dupont soybean with an oleic acid con- Rissler, a senior scientist with the Union for based regulatory decisions.” Jeffrey L Fox tent of 85%. This variety was modified with Concerned Scientists in Washington, DC. an extra copy of soybean Δ12-fatty acid dehy- Pioneer is “offering an alternative to those Biofuel ‘Made in China’ drogenase under the control of the soybean existing methods” without much added ben- Collaboration between the Danish enzyme β-conglycinin promoter, which triggered efit to consumers, she says. Alan McHughen, producer Novozymes of Bagsvared, Beijing- silencing of the transgene and its counterpart a plant biotechnologist at the University of based China Petroleum and Chemical and endogenous gene. But the product fizzled California, Riverside, notes that: “Those

© 2010 Nature America, Inc. All rights reserved. All rights Inc. America, Nature © 2010 Cofco, the state-run agriculture company, will after the company encountered global regu- who already despise [genetic modification] produce three million gallons of ethanol a latory complexities associated with the crop’s will continue to do so, those who accept GM year for local consumption, using corn stalks and leaves from northeastern China’s corn marker technology, says Sanders. Markers will continue to do so, and most others won’t belt. The demonstration plant will test novel are used by crop developers to test whether even notice it, as it’s not a high-profile whole technologies, including Novozymes’ new genetic material is successfully transferred food with immediate consumer-recognized Cellic CTec2 enzymes, with a view to launch a to the host crop. In this case, DD-026005-3 benefit.” commercial facility by 2013. Cofco has been contained the Escherichia coli uidA gene, In the US, food companies aren’t required running a small pilot plant in Heilongjiang encoding β-glucuronidase as a colorimet- to label food derived from genetically engi- province for four years, but as a precondition for commercialization “we need more capacity ric marker, and the bla gene, encoding the neered crops, and generally don’t voluntarily to optimize our design and operation,” says enzyme β-lactamase as a selective marker do so. Guo Shunjie, general manager of Cofco’s that confers resistance to β-lactam antibiot- An April 2010 survey of 750 US consum- bio-energy and biochemical department. One ics (such as penicillin and ampicillin). ers asked this question: “All other things remaining hurdle is the inability to break down Pioneer’s new high oleic soybean targets the being equal, how likely would you be to five-carbon sugars abundant in lignocellulose, which make up 20–40% of the plant biomass. same oleic acid pathway as the 1997 version, buy a food product made with oils that had The new process could cut costs considerably, but it is hoped that use of a different marker been modified by biotechnology to avoid as it requires half the dose of enzymes needed gene, one imparting tolerance to an ALS- trans fats?” Seventy-four percent said they by other treatments to break down plant waste. inhibitor herbicide, will smooth the regula- were either very likely or somewhat likely to The partners’ goal is to produce cellulosic tory path. (The plant will not be tolerant to buy this kind of biotech food. However, in a ethanol at $2.25 a gallon, a price further ALS-inhibitor herbicides at the levels used in separate question, only 32% of those respon- pushed down by government tax credits to be competitive with corn-based ethanol, currently the field.) Sanders says he is “optimistic” about dents said they had a favorable impression of at $1.50–1.60 a gallon. “Since the trend to the 2012 regulatory goals. biotech food. The survey was conducted by lower carbon emissions is here to stay, it On Pioneer’s regulatory heels are two the International Food Information Council won’t be long before we break even,” Monsanto soybean products with modified Federation in Washington, DC. says Shunjie. Daniel Grushkin oil profiles, one with omega-3 fatty acids for Emily Waltz Nashville, Tennessee

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