BUSINESS
NEWS ANALYSIS
Transgenic cotton highlights patent issues Calgene's cotton, genetically engineered to be herbicide resistant, recently has taken a major step toward commercialization, and the move has brought more attention to a controversy over patents and their potential effects on development. The step toward commercialization, the first such for transgenic cotton, began when Calgene was granted nonregulatory status by the U.S. Department of Agriculture (USDA), thus allowing the cotton to be grown anywhere in the U.S. without special approval (C&EN, Feb. 21, page 8). With a gene inserted from a naturally occurring soil bacterium, Calgene's BXN cotton has been designed to be resistant to a bromoxynil herbicide, Buctril, produced by Calgene's development and marketing partner Rhône-Poulenc Ag, an affiliate of the French company Rhône-Poulenc. Agricultural chemical use on cotton is intensive, requiring about 20 million lb of herbicides and nearly as many pounds of insecticide per year on the 13 million acres planted in the U.S. The BXN system, says John L. Callahan, Calgene's senior vice president for cotton, has the potential of reducing herbicide usage by 9 million lb per year. USDA's recent decision on the BXN system was applauded by BIO, the biotechnology trade association, and by the National Cotton Council (NCC), the cotton industry association. It was also supported by a majority of respondents during USDA's public comment period. Contrary to the view that herbicideresistant crops are moves by pesticide producers to increase chemical usage, Callahan explains, these crops are being developed by seed producers to be part of integrated pest management programs aimed at decreasing pesticide use. "The concept is to make cotton lines that are tolerant to the more environmentally acceptable herbicides and move toward postemergent systems." However, the Union of Concerned Scientists and other groups oppose the cotton's commercialization because of the increased use of Buctril and because it will introduce new genes to the environment. For Calgene's cotton, the remaining hurdles to entering the U.S. market include Environmental Protection Agency registration of Buctril for use on cotton and a pending Food & Drug Administration review of Calgene's food additive petition. The petition covers marker 18
MARCH 14,1994 C&EN
genes in genetically engineered tomatoes, cotton, and rapeseed. Calgene anticipates reaching the market by 1995, after spending this year working with major growers to assess the BXN system and its cost competitiveness. Recent developments for the Davis, Calif.-based agricultural biotechnology firm have highlighted an issue that continues to rivet the cotton industry. That issue is whether an extremely broad 1992 patent on all transgenic cotton will give Agracetus, a subsidiary of W. R. Grace, a monopoly in the cotton industry. But, Callahan says the issue has become a "tempest in a teapot." And, there seems to be little hard evidence that Agracetus' actions to date bear out the fears running rampant. The companies closest to commercializing transgenic cotton and accounting for most of the cottonseed sold—Calgene, as owner of Stoneville Pedigreed Seed, and Monsanto, with its partner Delta & Pine Land—have royalty-bearing licenses under Agracetus' patent. Although no one will comment on the specifics of the licenses, Callahan says the terms are reasonable. "The important points are that [the patent] doesn't create a crisis, because Agracetus has offered licenses, and that we think that patents are important to the industry overall," he adds. Agracetus was awarded its patent in late 1992, but only recently have representatives from USDA, patent specialists, and others in the agricultural industry become vocal in their criticisms and, in doing so, have garnered much media attention. They argue in principle that the patent's extremely broad claims could stifle research, prevent new advances from moving to market, and hurt farmers' traditional practice of collecting seed from a previous year's crop. However, others are questioning who developed the technology and whether it is innovative enough to have warranted a patent. In response, Kenneth Barton, vice president for R&D at Agracetus, says that like all research advances, the patented technology was built on top of previously published research and that it is the role of the patent office to determine whether a patent is warranted. Agracetus also says that it acknowledged its collaborators, specifically Norma Trolinder (now with USDA), in its patent application. "The reality is that the patent claims
aren't all that unusual," says Barton. "[But they are], at this time, unique in agriculture as there hasn't been all that much patent activity of this type until recently." This situation is unlike biopharmaceuticals, or biotechnology in general, where precedents have been set and where initial patents in new areas traditionally are broad and are followed by ones that are increasingly more focused. The archetypical case is that of the 1980 patent awarded to Stanford University and the University of California—based on the work of Stanley N. Cohen and Herbert W. Boyer—that generated similar fears of monopolies because it covers any use of recombinant DNA. In administering the patent, Stanford has offered a very accessible licensing program under which hundreds of companies now hold licenses, including the agricultural biotechnology companies. Ironically, one of the individuals frequently cited as expressing concern over Agracetus' broad patent claims is a law professor at Stanford University. Agracetus has stated that it intends to follow the normal policy of making available research licenses free of charge to all academic or government researchers, such as those at USDA, upon request "to assure their publicly funded research will be unaffected by this patent." And, it continues to discuss commercial licenses with other interested parties. It also is Agracetus' strategic decision, says Barton, for the company to focus on developing cotton with special fiber qualities. More than a year ago, the claims in the cotton and a related patent were reexamined by the Patent & Trademark Office, says Barton, which found the challenge without merit. The patent office will not comment on patent examinations, challenges, or the breadth of patent claims. Barton and many other observers agree that it is quite possible the patent will be challenged again, although no one at this point appears to have taken on the task or the expense to do so. Any challenges also may depend on whether Agracetus decides at some point to take a more protective stance. In reality, it still is very early in the development of transgenic cotton, and its potential and all the related issues have yet to be fully realized or played out. Maybe even more important is whether precedents are being set that will apply to other crops for which new technology is being developed and patents applied for. Ann Thayer
