Sequence Of Events

The following time line, detailing events relating to Genome Technologies' suit against Bento Soares and cDNA sequencing efforts in general, was culled from interviews conducted by The Scientist as well as information contained in court pleadings, statements, and media reports. The Integrated Molecular Analysis of Genome Expression (IMAGE) Consortium forms as an informal, ad hoc collaboration among colleagues to freely share complementary DNA (cDNA) libraries. The consortium is started by Greg Lennon, a senior scientist at Lawrence Livermore National Laboratory (LLNL); Charles Auffray, research director at the Centre National de la Recherche Scientifique in Villejuif, France; Bento Soares, an assistant professor of neurogenetics at Columbia University; and Mihaelis Polymeropoulos, a genome researcher at NIH. Genome Technology Inc. is founded by Soares; James Sikela, an associate professor of pharmacology at the University of Colorado, Denver, Health Sciences Center; and venture capitalists John Antretter and John Kaweskie, Jr. Science reports (R.F. Service, 263:1559-1510, 1994) that Johns Hopkins Oncology Center colon cancer researchers Bert Vogelstein and Ken Kinzler find information in a private database that leads to the discovery of a second colon cancer gene. The database is owned by Human Genome Sciences (HGS), a Rockville, Md.-based biotech firm, and its nonprofit partner, The Institute for Genomic Research (TIGR) in Gaithersburg, Md. Vogelstein and Kinzler access the TIGR/HGS database through a specially tailored agreement that would allow HGS first option at commercializing any results. Genome begins negotiations with Columbia, according to court documents on both sides. Genome's complaint states that the negotiations involve "licensing defendant Soares' technology on an exclusive basis," while Soares's answer states that the "plaintiff began negotiations with Columbia University regarding the licensing of certain technology." Also, according to Genome's complaint, between January 1994 and the start of the suit in spring of 1995, without Genome's knowledge or consent, Soares, "for the purpose of diverting a corporate opportunity . . . secretly continued negotiations with Columbia University to enter into an agreement with Merck." In Soares's answer, he denies these allegations, with the exception that he did have discussions with Merck during that time with "the knowledge and approval" of Genome. Vogelstein and colleagues publish a paper describing the isolation of the hMLH1 gene, which plays a role in a high percentage of colon cancer cases (N. Papadopoulos et al., Science, 263:1625-9, 1994). The research was conducted using the TIGR/HGS database. According to Alan Williamson, vice president of research strategy worldwide at Merck & Co. Inc., the idea for the Merck-Washington University (WU) genome sequencing project coalesces. The project is an effort to sequence human cDNAs and deposit the information in the public domain. Merck officials learn of the IMAGE Consortium, according to Williamson. As stated in Genome's complaint, Soares and Sikela meet with Merck on behalf of the biotech firm, with the "express purpose of developing a collaboration between the two companies." In Soares's response to the complaint, he acknowledges having discussions with Merck "with the knowledge and approval of Genome," but does not state when the discussions occurred or what they were about. According to Genome's complaint, Soares, while negotiating for Genome with Columbia, entered into discussions with Merck about his and Columbia's participation in the WU-Merck sequencing project. Soares acknowledges having discussions with Merck "with the knowledge and approval" of Genome, but does not state when the discussions occurred or what they were about. Soares resigns as director of Genome. October 1, Merck announ its public-domain sequencing project. Almost simultaneously, HGS, TIGR, and their financial backer and Merck's business rival, Philadelphia-based SmithKline Beecham, announce they will make available their private database of 35,000 cDNAs to university scientists. A few days later, HGS and TIGR release the details of terms for academic scientists wishing to access information from the database: Investigators must relinquish to HGS the first rights to potential products and the right to comment on scientific manuscripts derived from the cDNA database. Science reports (E. Marshall, 266:208-10, 1994) that the details of the WU-Merck project had not been finalized at the time of its October 1 announcement: Merck was ready to sign contracts but hadn't worked out legal arrangements with Columbia, which was "seeking reimbursement for the use of Soares's cloning technology." In the Science article, Columbia spokeswoman Elaine Metcalf confirms that negotiations were under way and that National Center for Human Genome Research director Francis Collins encouraged Columbia "to help create a public EST database." Soares and colleagues publish a paper on the normalization technique using human infant brain cDNA library (M.B. Soares et al., Proceedings of the National Academy of Sciences, 91:9228-32, 1994). Soares resigns as Genome's executive vice president of research. Sequencing begins at the WU-Merck project. LLNL issues a press release spelling out IMAGE's contributions to the WU-Merck sequencing project. WU and Merck announce the deposit of their first installment of 15,000 expressed human gene sequences into public databases. Daniel A. Conti, attorney for Genome Technologies, files a complaint with the United States District Court, Southern District of New York, against Soares. Columbia University issues a press release stating that the university donated cDNA libraries developed by Soares to LLNL. Also stated in the release: Columbia retains the right to license other libraries to companies if, "for the sake of time, they are not willing to wait until they become available in the arrayed configuration [an efficient organization scheme for cDNA clones]," and that the university has a patent pending on Soares's cDNA technology. According to the May-June issue of Human Genome News, the DOE and NIH newsletter of the Human Genome Project, as of June 27, 154,669 of the 206,654 human clone-derived expressed sequence tags in dbEST (a public-domain database) are from IMAGE clones, the bulk of which are based on Soares's cDNA libraries. Conti sends a press release to The Scientist, Human Genome News, and other publications summarizing the allegations against Soares. In the release he states that "after Dr. Soares co-founded the company and encouraged outside investors to invest in the company, he stopped working for the company, took his clone libraries and gave them to IMAGE." Soares's law firm files an answer to Genome's complaint in the United States District Court for the Southern District of New York on August 7. At press time, a trial date had been set for November 17. -K.Y.K (The Scientist, Vol:9, #19, pg.7 , October 2, 1995) (Copyright © The Scientist, Inc.)

Sequence Of Events

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