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Sharing the Glory, Not the Credit

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Science  16 Feb 2001:
Vol. 291, Issue 5507, pp. 1189-1193
DOI: 10.1126/science.291.5507.1189

Greeted by chamber music and an honor guard, leaders of the public and private groups sequencing the human genome filed into the White House last June, shook hands with the president, and pledged to support each other's endeavors. Within weeks, this show of amity dissolved. Over the summer and fall, the teams withdrew to their labs, muttering about the doubtful quality and accessibility of each other's research. The grumbling continued until December, when the two decided to part company at the finish, collaborating only on a single publication date. The result: Two reports on the human genome are coming out this week—a privately funded version in Science and a publicly funded version in Nature.

The falling-out over the final reports is just a footnote to the huge effort to complete the sequencing of the human genome. But it highlights a philosophical disagreement over how such data should be shared (see sidebar on p. 1192). It also reveals how the rules of scientific publishing, usually rigid, become flexible when the stakes are high. Journal editors are accustomed to telling authors what a paper must disclose and what kind of supporting data must be released. But in this case, the authors themselves—because they were offering a big prize—sought to write the rules. Scientists in the public sequencing group also sought to shape the rules that would apply to the paper from the rival private group. As they courted the authors of these hot papers, the journal editors invited comments on data release, received sharply clashing recommendations, and chased an elusive consensus.

The imbroglio, which reached a peak in the last few months, first broke into public view in March 2000. At that time, the private genome group—headed by J. Craig Venter, president of Celera Genomics in Rockville, Maryland—was still discussing the idea of pooling data and publishing results with the public group, headed by Francis Collins, director of the U.S. National Human Genome Research Institute. Several public-group scientists led by Eric Lander, director of the Whitehead/MIT Genome Center in Cambridge, Massachusetts, had spearheaded efforts to work out a compromise. But the talks broke down.

That failure became evident when an official at the Wellcome Trust, the British charity that supports one of the largest nonprofit sequencing teams, the Sanger Centre in Hinxton, U.K., leaked a letter to the press from Collins to Venter (Science, 10 March 2000, p. 1723). In the letter, Wellcome officials and U.S. scientists charged that Celera was trying to maintain control over the jointly produced genome data for 5 years and claim intellectual property rights on uses of those data in secondary technologies, such as gene chips. When Celera did not respond quickly, the publicly funded scientists declared the negotiations over. They had insisted that data be deposited immediately in a public database, with no commercial conditions attached. Celera wanted to guard against data piracy by retaining the information on its own Web site, with certain restrictions: Users would not be able to resell the information or use it for other commercial purposes.

Addressing a congressional hearing on 6 April, Venter denied that he wanted exclusive control of the genome data. “We will release the entire consensus human genome sequence freely to researchers on Celera's Internet site when it is completed,” he said. But the public group leaders say they had trouble nailing down the details of Celera's conditions on how its data could be used.

By the time of the much-publicized June ceremony at the White House, the two groups had stopped talking about a pooled database and agreed to “coordinate” but not to collaborate, as Collins explained in June. Collins and Venter still held out hope that they might release their reports in the same journal. At the time of publication, Collins and Venter explained in June, the public group would deposit its sequence data in the free public database GenBank, whereas Celera would release data through its own Web site.

Science and Nature were competing for the papers, and the authors let both journals know that they were looking for the best terms. In June, Donald Kennedy succeeded Floyd Bloom as editor-in-chief of Science, taking charge of months-old negotiations. Members of the public consortium had by then made abundantly clear that they did not want Science, or Nature for that matter, to allow Celera an exception to the traditional practice that genomic data be released in GenBank. One respected scientist in this field who asked to remain anonymous says that “jealousy” over scientific credit played a big part in the split.

Man in the middle.

Science Editor-in-Chief Donald Kennedy received a barrage of e-mails about the terms for publishing the Celera paper.


“I got a very thoughtful memo from Eric Lander” about publishing genome data, Kennedy recalls. It laid out “three or four license terms that he thought would not be reasonable and a general one that he thought would be OK.” Serious negotiations began in September, with editors at Science running between the two camps. Editors worked out what they viewed as a balanced plan, requiring Celera to release data freely to academics but allowing the company to protect its database by requiring readers to obtain access at a company site and register as academic or commercial users. Nonprofit scientists would have free access, Celera said, but those with commercial connections would have to pay. Commercial users would also be bound by other intellectual property conditions.

Leading critic.

Harold Varmus believes the protests improved the terms for access to Celera's data.


Lander objected to these terms as “discriminatory” and “absolutely unacceptable,” says Kennedy. Lander declined to comment publicly, saying he wanted to see the final terms (which were being finalized at the time; see sidebar). Colleagues say he argued forcefully in November that authors of scientific papers must share data freely with all readers—not just with academics. Biotech scientists, several people argued, would find it impossible to accept Celera's terms and would be excluded from examining the results. Harold Varmus, former director of the National Institutes of Health (NIH) and now president of the Memorial Sloan-Kettering Cancer Center in New York City, is sympathetic to Lander's view. “This is a complicated world now,” Varmus says. “It's not just people in industry who have commercial connections; many people in academia do.” Whitehead/MIT Genome Center scientists, for example, are involved in a 5-year consortium—funded by Affymetrix Inc. of Santa Clara, California; the Bristol-Myers Squibb Co. of Princeton, New Jersey; and Millennium Pharmaceuticals of Cambridge, Massachusetts—that aims to put genomic information on digital chips.

In October, Kennedy solicited advice from several other experts, who identified previous scientific papers in which readers were required to obtain supporting data from an independent Internet site. Some limited free access to nonprofit scientists. “This horse had already left the barn,” Kennedy concluded. This interpretation prompted a new uproar in late October.

Members of the public genome project mobilized opposition. Warnings poured in to Kennedy by e-mail from well-known biomedical researchers, including molecular biologist Marc Kirschner of Harvard University; Bruce Alberts, president of the National Academy of Sciences (NAS); and Varmus. Varmus's letter, dated 5 November, was co-signed by other heavyweights, including David Baltimore, president of the California Institute of Technology in Pasadena; J. Michael Bishop, chancellor of the University of California, San Francisco; Arthur Levinson, CEO of Genentech in South San Francisco; Edward Scolnick, president of Merck Research Labs in Rahway, New Jersey; Kenneth Shine, president of the Institute of Medicine in Washington, D.C.; and Maxine Singer, president of the Carnegie Institution in Washington, D.C. They wrote to “express our concern” that Science might allow authors of an unspecified paper to “restrict availability” of the raw data. Doing so, they argued, might “open the door to similar withholding of information by future authors, with unfortunate consequences. …” They urged Science to get more advice before taking this “unprecedented step.”

Kennedy says he weighed the advice and criticism. Science's editors consulted with an intellectual property expert at NIH and with Tom Cech, president of the Howard Hughes Medical Institute in Chevy Chase, Maryland, a nonprofit organization that had already agreed to subscribe to Celera's private database. In a conference call, Kennedy received encouragement from Harvard chemist George Whitesides, molecular biologist James Hudson of Research Genetics Inc. in Huntsville, Alabama, geneticist Nina Fedoroff of Penn State University, and a half a dozen others. After proposing additional improvements in the terms of data release—including the use of materials transfer agreements that would let viewers have free access to the data but give Celera legal protection against data piracy—Kennedy decided that the terms were fundamentally acceptable.

At this point, bioinformatics leaders raised objections. On 6 December, a former member of Science's board of reviewing editors, geneticist Michael Ashburner of Cambridge University, distributed an open letter to these editors, urging them to quit and boycott Science. Another board member, cancer researcher Bert Vogelstein of Johns Hopkins University School of Medicine in Baltimore, Maryland, circulated a reply, saying he believed the final agreements “will meet the standard of public access to data that has been and continues to be Science's policy.” The next day, leaders of the public genome project voted to end discussions with Science and submit their paper to Nature (Science, 15 December 2000, p. 2042).

The decision to send the paper to Nature was not unanimous: Ari Patrinos, director of the U.S. Department of Energy's office that funds genome research, says, “It's no secret that I was advocating back-to-back publication in one journal, Science.” But British members of the consortium were outraged by the deal with Celera. Lander adds: “We had to choose between two journals, and Science's policy [on data release] wasn't clear.” Although Nature's editors haven't ruled out the use of private databases, the public consortium decided, Lander says, that it was “an easy choice” to submit a paper to them.

Varmus says that he believes the letters, including his own, improved the terms of data access. He recognizes that Celera cannot give away information it has spent hundreds of millions of dollars to acquire. But he argues that publishers need to find new ways to make data from private ventures available, because we are “now in an era of heightened commercialism” in which a great deal of genome and protein structure data will be in private hands. Says Patrinos: “This issue is not going to go away.” Varmus hopes this episode will prompt a formal review—perhaps at the NAS—of “what publication really means.”

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