Immunex Case Could Shake Up Peer-Review Process

For years, universities and corporate research labs alike have revered a practice called peer review. One scientist reads and critiques another's research paper before publication, with the aim of bringing an objective eye to the originality and strength of its finding.

But what happens if a paper contains an idea that's commercially valuable? People submitting papers for review have long assumed that lifting the idea would be unethical, a violation of trust. But would it be illegal?

That's the issue at center stage in a closely watched lawsuit that is getting under way in Seattle. Cistron Biotechnology Inc. of Pine Brook, N.J., is alleging that a key idea was stolen during peer review and used to win a patent for the defendant, rival biotechnology company Immunex Corp. Immunex, based in Seattle, has denied wrongdoing.

It's an unpleasant rub in the growing alliance between life science and business: Science's tradition of peer review of unpublished material, with its assumption of confidentiality, is more and more at odds with the dog-eat-dog world of business, where corporate espionage can be a way of life.

"The potential implications of this case are enormous," says Drummond Rennie, deputy editor for the Journal of the American Medical Association. "The peer-review process, like the whole of science, depends on trust," he says. "If in this case it's judged OK to steal from other peoples' belongings when those belongings are out for review, then the review process is in real trouble."

Going to court

Researchers say review violations have occurred periodically for years but always have been handled by ethics committees at universities or federal agencies such as the National Institutes of Health. Lawyers say this case, scheduled for trial in September, is the first time the knotty question has landed in court.

Lawyers for both sides declined public comment on the case, in which Cistron is seeking $100 million in damages. But from their court filings, it is possible to piece together their positions.

Cistron accuses Immunex of theft of trade secrets in misappropriating a chemical sequence for a gene that makes Interleukin-1, or IL-1, a protein that plays a key role in regulating the body's immune system. Immunex then used that information to win a patent.

Cistron alleges that in 1984, Steven Gillis, who was then head of research at Immunex, was asked to do a peer review of a paper that Cistron had submitted to the science journal Nature. Cistron says the paper detailed the IL-1 gene and the protein it produced and that Gillis took the gene sequence from the paper and used it to file and eventually win a patent on the gene. (Gillis has since left Immunex to work for another biotechnology company.)

At the heart of Cistron's claim of theft is that seven errors that Cistron made in recording the chemical sequence of the gene appeared as well in the gene sequence that Immunex submitted to the U.S. Patent Office.

The chance of those errors - Cistron is calling them "fingerprints" - occurring by chance, scientists on both sides agree, are slim.

For its part, Immunex acknowledges that the Cistron sequence was used in the Immunex patent application and says this was because of a clerical error. But it denies that it misappropriated anything. Court papers suggest that Immunex will argue that the rules of peer review are so ambiguous that the process carries no obligation of confidentiality or protection.

The filings also indicate that Immunex will argue that Cistron lost any claim to intellectual-property protection when it sent its paper out for peer review and flashed the gene sequence on a screen for several seconds at several science conferences and that, in any case, what Immunex discovered is different from what Cistron discovered.

Scientists worry

However the case is resolved, some scientists worry it could have a chilling effect on scientific cooperation. "If Cistron wins, it will be creating new law, namely that expectation of confidentiality creates a cause of legal action," says Stephen Bent, a patent attorney who has Immunex as a client, though not for this case. "My feeling is that this could make people very reluctant to get involved for peer review."

William Ryan Jr., chief executive of OncorPharm, a subsidiary of Oncor Inc. in Gaithersburg, Md., says the message is: "The only safe and reasonable conduct is to write your manuscript and your patent application at the same time."

Ryan and others say one likely outcome will be new laws, either at the state or federal level, spelling out the relationship between peer review and intellectual property.

In addition, publications may make reviewers sign written contracts pledging secrecy, or they might warn submitters that they risk material passing to competitors.

"A focus will be on journal editors, who should be thinking of setting up procedures to ensure reviewers aren't in a position to profit from advance notice of information," says Edgar Harold, a professor of law at Columbia University.

"There is an unwritten ethic that you should not . . . make use of the information. Whether the unwritten rules will become written - it could very well come to that," says Richard Burgess, director of the University of Wisconsin Biotech Center.