WASHINGTON _ Despite Wall Street's apparent lack of enthusiasmfor agricultural biotechnology, the field has been quietly exploding inits scientific and commercial potential.A sampling of presentations from the annual American ChemicalSociety's (ACS) national meeting here revealed promising research ona range of targets for genetic tweaking: from yeast cells (to brew beerfaster) to bacteria (to remove sulfur from petroleum more efficiently)to catfish (to improve cold water tolerance) to soybean seeds (toproduce pharmaceutical-grade proteins and peptides).Even as pie-in-the-sky research is conducted in obscure laboratories,real products are hitting the shelves of supermarkets. Calgene Inc.'sFlavr Savr tomato, the first genetically engineered whole food availableto consumers, was approved by the FDA three months ago. Thecompany claims that demand from consumers and retailers hasoutstripped all expectations.A certain momentum appears to be growing and researchers at an ACSforum on genetically modified foods and other products spokeenthusiastically about the future. "A technological revolution is takingplace," said Alvin Young, director of the Office of AgriculturalBiotechnology at the U.S. Department of Agriculture (USDA).Seeds As BioreactorsResearchers at Agracetus Inc., in Middleton, Wisc., want to use MotherNature's storage technology, seeds, to produce complexbiopharmaceuticals for conditions such as breast cancer and hepatitis.Once owned by Cetus Inc. (which merged with Chiron Corp.),Agracetus is now a wholly-owned subsidiary of W.R. Grace & Co.According to David Russell, director of plant molecular biology atAgracetus, the company is collaborating with Bristol-Myers Squibb toproduce an anti-cancer monoclonal antibody, BR96, in plant seeds.BR96 is currently produced using traditional mammalian cell culturetechnology."There is no cheaper way to make proteins than in plants," saidRussell. "Viral pathogens and other problems that arise withmammalian cell culture fermentation are not an issue with plantmaterial."Agracetus researchers use a "gene gun" to shoot foreign genes into aplant such as corn or soybean. The borrowed gene typically would becloned from a human tissue sample into an E. coli bacterium. Aftersubsequent manipulations in E. coli, the gene is coated ontomicroscopic gold "bullets" and injected into corn or soybean cells. Thetransplanted gene causes the plant to produce the desired product,hopefully a valuable protein, and to accumulate this material in itsseeds. The ability to produce the protein is passed on to successivegenerations of the plant, which can be cultivated in a field to scale upproduction."If we use plants as bioreactors in this way, novel enzymes could beproduced in high quantity in the seed of major crops," said Russell. Ofcourse, the critical and final step in this process would be the extractionand purification of the proteins from the plant biomass. Russellconceded that this step, which would be governed by GoodManufacturing Process requirements, could add considerable expenseto the plant production method.Nevertheless, he maintains that transgenic plants could one daychallenge the predominance of bacterial and mammalian cell culturefermentation technology as the preferred means of production ofproteins and peptides. Russell said that "in today's climate of trying tolower drug costs" any technology that can significantly lower the costsof production will be prized."Better Beer Brewing FungiiResearchers from Kirin Brewery in Yokohama, Japan and the BerlinUniversity of Technology in Germany have genetically modified yeastcells to shorten the beer-making process. Yeast is used during beerfermentation to produce alcohol as well as to impart several flavorcompounds. However, one of the flavors produced during this processis unpleasant, which means that two to four weeks of additionalmaturation time is needed in order for the offending flavor to mellow.The trouble appears to be a substance, called alpha-acetolactate, leakedby yeast cells during fermentation and then converted into diacetyl, acompound that gives beer an unpleasant "buttery" taste. Japaneseresearchers, led by the general manager of Kirin Brewery's CentralLaboratories for Key Technology, Reisuke Takahashi, modifiedbrewer's yeast so that the diacetyl by-product is made in lesserquantities. The German team, led by microbiology and geneticsprofessor Ulf Stahl at the Berlin University of Technology, created amodified yeast strain that produces no diacetyl.Stahl's group transferred the alpha-acetolactate decarboxylase (ALDC)gene from the bacteria Acteobacter pasteurianus into brewer's yeast.This enabled yeast cells to convert the alpha acetolactate into aflavorless substance known as acetoin, instead of into the unpleasantlyflavored diacetyl. "Subsequent maturation was unnecessary when usingsuch a genetically modified yeast strain," said Stahl. Stahl said thatpublic opinion in Germany was opposed to using gene technology,particularly in breweries, but that the new yeast strain could be usedsoon in Central and South America.FDA To Propose New Rule ForGenetically Engineered FoodsThe FDA has drafted a pre-market notification (PMN) regulation forgenetically engineered foods that could be published in the FederalRegister within six months. Details of the policy are not known andcould still change during an extensive interagency review process nowunder way.James Maryanski, strategic manager for biotechnology from the FDA'sCenter for Food Safety and Applied Nutrition, confirmed at the ACSmeeting what many in the agricultural biotechnology industry havebeen expecting for about a year now _ that a formal PMN rule forgenetically engineered food products is on the way. Currently,companies consult with the FDA on a voluntary basis about geneticallyengineered foods they are developing.The FDA has already sent its draft PMN proposal up the bureaucraticchain of command for evaluation. The first stop will likely be thePublic Health Service, another branch of the Department of Health andHuman Services. After that, the Environmental Protection Agency, theDepartment of Agriculture and the Office of Management and Budgetall are likely to mull it over. If cleared, the proposed regulation wouldbe published in the Federal Register followed by a period of publiccomment.FDA and biotechnology industry representatives have met repeatedlyto discuss the content of the proposed PMN rule, most recently on July8. However, no one has actually seen the document. Simon Best, CEOof Zeneca Plant Science and vice chairman of the BiotechnologyIndustry Organization's food and agriculture division, said that theFDA must reconcile any new PMN rule with the agency's currentpolicies on genetically engineered foods.Best said current FDA policy states that transgenic plants are anextension of basic plant breeding techniques and do not pose new risksto consumers. "We don't want to set a precedent that suggests there issomething different about these foods," Best told BioWorld. "We wantto make sure that pre-market notification does not expand into a fulldata approval process . We are happy to comply with anything thatdoesn't contradict current policy." n
-- Lisa Piercey Washington Editor
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