A Scrap over Sequences, Take Two

Science magazine's controversial decision to publish the Syngenta draft rice genome sequence without requiring the company to deposit its data in a public database is getting less than rave reviews from scientists who need to use the genome map in their work. Over the objections of leading scientists who warn that scientific publishing principles have been sacrificed to commercial gain, Science allowed the agrochemical giant based in Basel, Switzerland, to maintain control of its data when it unveiled its draft blueprint of the japonica strain of rice in the journal's April 5 edition.1 Syngenta declined to deposit its data in GenBank, the open public storehouse of genetic material. A Chinese-led team of academics published a blueprint of the indica strain of rice in the same issue, and that map will be available on Genbank.2 "It's a fundamental principle of scientific publication that you provide the data and that science can build on it," says Robert H. Waterston of the Washington University, one of 19 leading scientists who signed a letter protesting Science's special arrangement with Syngenta. "This has been a procedure that has worked very well over several hundred years." The journal's editor-in-chief Donald A. Kennedy says Syngenta had set up a system of data access that met Science's standards, including what seemed to be open release to academic researchers. The compromise, he says, was necessary to give academic researchers as much access as possible to the genetic data for the most important food crop in the developing world. "I think it's a good deal for the scientific enterprise, for science with a small s," Kennedy says. Steven Briggs, head of genomics at Syngenta and president of the Torrey Mesa Research Center, presented the company's solution as an "innovative access program that balances humanitarian and commercial benefits." Syngenta's intent, he told a press conference announcing the program, is to "provide the rice genome map at no cost to the world's researchers." Courtesy of Wellcome TrustJohn Sulston Nevertheless, for many scientists, the magazine's agreement with the biotechnology company spells a loss of access. Critics of the arrangement advise researchers who need the genome information to use material published on the indica strain or wait a year to 18 months for the Syngenta and the Chinese team to complete maps for deposit in GenBank. John Sulston, former director of the Wellcome Trust Sanger Institute in Britain and one of the leaders of the public research team that competed with Celera to sequence the human genome, predicted that private data arrangements would continue, boosting the cost of producing food grains, drugs, and therapies. "This is part of the general movement of intellectual property law, which is tending to reinforce the position of the rich nations, America and Europe," he says, "which are involved in a constant seizure of intellectual property in a process that gives them what amounts to a patent by the back door." Stunted Chunks Critics say Syngenta is dribbling out data in impractically small chunks or releasing it in a form that makes it difficult for scientists to do cross-species research vital to genetics advances. Academic researchers can download only 100 kilobytes of sequence information per week from the Web site of the Torrey Mesa Research Institute, a Syngenta subsidiary. That's not enough to do any real work, especially with the search engine provided, says Pamela Ronald, a rice geneticist at University of California, Davis, and one of the first academics to try to tap Syngenta's database. "There's no control on the stringency of the search," the rice researcher says. "You use up your entire allotment for one week in one search and there is no way to fine-tune it." The Syngenta deal was Science's second break with scientific publishing tradition. In 2000, Celera Geonomics published its sketch of the human genome under an arrangement that allowed it to safeguard its data.3 Celera now collects about $100 million annually in licensing fees. Like the deal Science cut with Celera, the Syngenta arrangement does not allow free-range research, some say. Syngenta has promised to give academic scientists who need bigger chunks of rice gene data the entire unannotated draft sequence on a CD-ROM. That's not good enough, according to Sulston. "Although it seems generous, in practice, a lot of the sort of research that people want to do involves scrounging through things and going to and fro," Sulston says. Syngenta's terms make it tough, if not impossible, for genetics researchers to maneuver at will, he adds. "Bioinformatics is an indivisible subject because there is a constant advantage in comparing one thing with another." Crossing Data Boundaries GenBank, in contrast, is set up to permit simultaneous searches across a number of species, a function considered vital. Nightly, GenBank operations in Maryland, Britain, and Japan swap data to make sure any researcher who wants to do a BLAST search across the entire store of genetic knowledge can do so, for example. "Free means free," says Sir Aaron Klug, the 1982 Nobel Laureate in chemistry who added his name to the protest letter. "Free isn't just about cost, but it means freely available in its entirety, which was what was happening with the public databases." The terms of the Syngenta releases could make it tough for academics to get the institutional co-signers they will need to get the CD-ROM, the critics say. Syngenta wants academics to guarantee they will use the data for only noncommercial research. How this restriction fits with the company's insistence that academic scientists can patent and license their work is unclear. Syngenta and Science respond with assurances that, case-by-case, problems will be resolved and science will be served. Syngenta spokesman Christopher Novak writes in an E-mail: "My sense is that if they are conducting research that is not being funded by, or done at the behest of, a commercial entity, then any commercial developments belong to the researcher [or the] institution and may be developed, licensed, [or] sold." Steve Goff, Syngenta genome technology director wrote in an E-mail to users of the rice gene data acknowledging that some problems had cropped up, but said the company had worked to resolve them. Researchers question how any scientist can sign away potential commercial uses of information, sight unseen, when academic scientists are under pressure to produce commercially exploitable work. "The giving of an affidavit that the access is absolutely not for profit is incompatible with people's working lives," Sulston says. But scientists fear that the Syngenta deal, coming on the heels of that with Celera, foreshadows a dismantling of openness in science, integrity in research, and courage in publishing. Sir Robert May, the Oxford professor who presides over Britain's Royal Society and sits on a special advisory panel at Science, says the deal was a bad but almost inevitable consequence of Science's "negotiating error" in dealing with Celera and its founder, J. Craig Venter. "He really needed that publication," May says. "And [perhaps] he would have blinked first if he had been dealing with tough negotiators who had unfailingly in mind for the sake of the science, for the sake of the subsequent industry, and for the sake of the sheer moral principle that it should bloody well have been put in the public database." At the press conference related to the Syngenta publication, Kennedy pointed to 800 million people who lack adequate food supplies, and predicted the rice genome would do more good for humanity at large than has the human genome map. Weighed against those considerations, Kennedy said, allowing Syngenta to tailor access to protect its investment was not a major sacrifice. But David Lipman, director of the National Center for Biotechnology Information in Maryland, the US home of GenBank, calls explanations like Kennedy's "self-fulfilling" prophecies. "If you make [holding back data] an option, companies will take it. It's interesting that they define the slippery slope that they're sliding down as a new peak. There's something quite irritating about that." Sulston says Kennedy's "singing violins simply don't wash at all. There's perfectly good rice data out there." He predicts that the Celera and Syngenta deals are the start of a trend toward producing unwieldy commercial databases. "I see an immediate reduction of value in the short run from every single submission that does not go to GenBank," the scientist says. "But much more serious in the long run is the possibility that this could lead to highly dispersed and fragmented databases that cannot be searched efficiently." Despite concern expressed by scientists like Sulston, shareholders rallied at the news of the deal and Syngenta's stock price climbed steadily as the Science article neared publication. Early in the year, Syngenta hovered around $11 per share in relatively low-volume trading on the New York Stock Exchange. A late March press release announcing the pending publication triggered trading at seven times the normal volume, a mark that investors are excited about a stock. The day before the Science press conference, Syngenta's stock hit its highest price in 12 months, $13 per share. The day Kennedy and Syngenta genomics chief Steven Briggs manned the mikes for humanity at the press conference, Syngenta held most of the gains to close at $12.85 per share. Peg Brickley (pegbrickley@hotmail.com)is a freelance writer in Philadelphia. References 1. S.A. Goff, "A draft sequence of the rice genome (Oryza sativa L. ssp. japonica)," Science, 296:92-100, April 5, 2002. 2. J. Yu et al., "Draft sequence of the rice genome (Oryza sativa L. ssp. indica)," Science, 296:79-92, April 5, 2002. 3. E. Russo, "Behind the sequence," The Scientist, 15[5]:1, March 5, 2001.

A Scrap over Sequences, Take Two

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