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The Power of Negative Thinking

January-February 2003

Doing science is always more fun when your predictions prove true and your experiments shine. Positive results are satisfying, significant, even lucrative, and scientists labor long and hard to get them. Like baseball sluggers stepping up to the plate, many scientists hope for home-run outcomes and dread research slumps for good reason: swing and miss too often and maybe your contract, or your funding, won't be renewed.

Although ball players can't win with bad batting averages, scientists often learn from a good whiff, says Hersey professor of cell biology Bjorn R. Olsen. Many experiments fail, or produce controversial, ambiguous, or unexpected results. For those who bravely—or accidentally—go where few have gone before, Olsen and Christian Pfeffer, a visiting research fellow in pediatrics at Dana Farber Cancer Institute, have created the Journal of Negative Results in Biomedicine to push such outcomes into the mainstream.

Christian Pfeffer and Bjorn Olsen
Christian Pfeffer (left) and Bjorn Olsen find value in studies that don't pan out.
Photograph by Jim Harrison

"The word 'negative' is a little bit misleading," says Olsen, who edits the Web-based journal. "You have to see it in context. Anything different from what you expect is, on the surface, negative." Yet scientists regularly push negative findings aside, blaming them on shoddy procedures; some researchers bury the results deep in papers, with little explanation, if they publish the material at all. Pfeffer became frustrated by such wasteful behavior and searched for a way to recast negative results. Two colleagues rejected his journal concept before he found a collaborator in Olsen.

The classic negative result is an experiment that shows no difference between experimental and control groups: for example, a clinical trial of a drug that works on mice, but turns out to have no effect when tested on humans. Or genetics researchers seeking a certain disease-causing gene might fail to find their target, but might still be able to rule out a number of other genes within a defined chromosomal region, thus helping to narrow future searches. "To prevent duplication of effort and save public money, it doesn't make sense for everyone to go through the same gene-sequencing effort," says Olsen. "Getting credit for a negative finding will speed up the rate at which genes get identified."

Ambiguous or controversial results, or outcomes that challenge entrenched ideas, are also considered negative sometimes. For Olsen and Pfeffer, scientific rigor is what sifts a valuable negative nugget from junk research. Reproducible results, obtained through rigid experimentation, are worth keeping, they say, regardless of the positive or negative spin.

What sort of research will fill the Journal of Negative Results? Olsen describes geneticist Barbara McClintock's findings on transposition, or "jumping genes," as the type of paradigm-smashing work he and Pfeffer hope to attract. McClintock's original research in the 1940s and '50s didn't support the widely held belief that genes were fixed on chromosomes. "In McClintock's case, the conclusion that genetic material could move around seemed totally at odds with the dogma that genes were remarkably stable and only very rarely underwent changes," Olsen explains. Her results were scorned and obscured for years, but eventually disproved the fixed-gene theory. McClintock won a Nobel Prize in 1983 for her work—and transformed scientific thought. "These [types of] results," Olsen says, "are so new and so different from what everybody expects that they are considered negative."

Not long after Olsen and Pfeffer began brainstorming, London-based BioMed Central, publisher of The Scientist and numerous on-line journals, offered them a contract. With that backing, they were able to ensure free on-line access to their journal's articles and to cross-reference them in databases like Pub-Med Central, a digital archive managed by the National Library of Medicine. The two have also assembled a review committee of respected scientists and doctors; traditional scholarly publishing can take weeks or months to present articles, but the Journal of Negative Results aims to streamline the process by publishing papers on line as soon as they pass muster.

A few other publications have nudged into negative territory, but they've been short-lived or narrowly focused. Olsen and Pfeffer have opened their journal to biology and biomedicine—a huge academic territory. Yet their concept still faces hurdles: some scientists have been reluctant to publish negative results for fear of damaging their reputations, others worry about aiding their competitors. The journal's first "issue," which appeared in September, contained only one article, but seven manuscripts were under review as this magazine went to press and five others had been rejected as insufficiently rigorous. For the two founders, indeed, the greatest challenge lies in building credibility. "In some ways," Olsen explains, "it's up to us as editors to define the line between what is rigorous science and what is sloppily done."