Last night, Harold Varmus appeared to me in a dream. Dressed in cycling garb, the Nobel laureate and former director of the National Institutes of Health was on a mission to rid the world of corks. This is not as foolish a quest as it might sound. In the dream, corks were plugging bath drains and kitchen sinks, clogging street gutters in miniature logjams, even getting stuck in people’s mouths. For Varmus, the moment had come to fight back.

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I had been spending some time with Varmus, so I was not surprised to find him in a dream of mine, wearing his biking outfit. At 66, he is an avid cyclist, as well as a jogger, hiker, and rower, and he loves to talk about his physical pursuits. His crusade against the corks makes sense, too. They’re a comically simple metaphor, courtesy of my rubelike unconscious, for a real-life struggle that has engrossed him since he left the NIH seven years ago and that has turned this icon of the scientific establishment into a powerful subversive.

Three days before the dream, I am walking with Varmus across Harvard Yard. We’re heading to the Berkman Center for Internet and Society, which has invited him up from Manhattan’s Sloan-Kettering Cancer Center, where he is president. It’s a cold, blustery day, but Varmus is wearing only a thin hounds-tooth sports jacket against the wind, which has whisked his sparse, reddish brown hair into a messy crest. He keeps his hands in his jacket pockets and a slightly strained smile on his face.

Varmus is the most visible characterin the movement to free the scientific world of its figurative corks: scholarly journals that restrict the flow of information by charging often hefty subscription prices for access to their content. Today, Varmus has been invited by Charles Nesson, a professor of law at Harvard, to enlighten the student editors of the various Harvard Law School journals about the virtues of so-called open-access publishing. Nesson introduces his guest as “the prophet of open access.” Varmus’ smile doesn’t fade, and his hair stands proudly where the wind last left it.

He calmly lays out his campaign. For centuries, journals have been the means both of disseminating scientific knowledge and building scientific careers. Accordingly, the journals atop the hierarchy draw the highest-quality submissions, which reinforces their lofty reputations, which in turn enhances the status of the scientists who publish there. This positive feedback loop puts the power in the hands of the journals, even though their existence depends entirely on the scientists who write, edit, and serve as reviewers, usually without compensation.

Meanwhile, their colleagues can gain access only through subscriptions that their institutions pay for, sometimes dearly. (A yearly subscription to Brain Research, for instance, costs more than $20,000.) Worse, most of the public – scientists in developing countries, faculty and students in underfunded colleges, high schoolers, patients – have no access at all, even though taxes fund the government grants that support much of the research. Varmus asks: Shouldn’t this ancient system have changed with the Internet, which allows information to be disseminated cheaply and immediately searched, mined, archived, reviewed, and improved?

He then opens the floor for discussion. The editors seem enthusiastic, if a little perplexed.

“We have a different situation, since the journal has its own institutional cachet,” says the editor of The Harvard Law Review, a graceful young woman in a sky-blue cashmere sweater. “I can’t imagine proposing to my board that we stop printing paper copies.”

“Printing paper copies of the journal isn’t inconsistent with open access,” points out Stuart Shieber, a computer science professor who is championing open access at Harvard. “What matters is whether you put your content up on your Web site, too, for free.”

“Oh, we do that already,” she says.

“Then in what sense aren’t you open access?” Varmus asks.

“Well, we only leave it up for a little while,” she replies. “Then we take it down. We have to, because of our agreements with other Web content companies, like Lexis-Nexis.”

“How much money are we talking about?” Shieber asks.

“I really shouldn’t be specific.”

“Ballpark.”

“Like, half a million?” (Later, she tells a Wired fact-checker it’s closer to $100,000.) People shuffle in their seats.

“So, what happens to that money?” Shieber asks.

The law review editor shrugs. “We keep it.” There’s a silence, like the sound of a cork not popping.

The exchange with the law review editor is a mere skirmish in a protracted war that Varmus and his comrades have been waging against the status quo. His early attempts to change scientific publishing and convince the scientific community of the virtues of open access fell flat. But that didn’t dampen his passion, and a recent effort has become a spectacular success.

Three years ago, through an organization he cofounded called the Public Library of Science, Varmus launched a set of journals, which survive not through subscriptions but by charging $1,500 to most authors (and thus their grant givers) whose articles are accepted for publication. Everything is then put online and kept there, freely accessible to anyone. Despite the newness of this model, research published in the flagship journals PLoS Biology and PLoS Medicine often finds its way to The New York Times or the BBC. Last June, less than two years after the first issue of PLoS Biology went online, Thomson Scientific, a firm that tracks citation rates, assessed the journal an “impact factor” higher than such established journals as Biological Reviews and Proceedings of the National Academy of Sciences. Indeed, in a phenomenally short time, it has become the most cited journal in general biology.

The success of the top two PLoS journals has led to the birth of four more modest ones aimed at specific fields: clinical trials, computational biology, genetics, and pathogens. And this summer, Varmus and his colleagues will launch PLoS One, a paperless journal that will publish online any paper that evaluators deem “scientifically legitimate.” Each article will generate a thread for comment and review. Great papers will be recognized by the discussion they generate, and bad ones will fade away.

“Our mission is to transform how science publishing is done,” Varmus says. “We aren’t trying to torpedo the industry. But we are definitely going to change it.”

Walking back to Harvard Square to pick up a cab, Varmus looks over his shoulder toward Wendell Street, where he lived 44 years ago when he was a grad student in English literature.

The son of a doctor and a social worker, Varmus grew up on Long Island, spending his free time on the beach or with his nose in a book. He entered Amherst College with a notion of becoming a doctor (too predictable), then tried on philosophy (too abstract) and physics (too hard) before earning his degree in literature (just right, it seemed then) and starting graduate studies at Harvard in 1961.

Varmus soon began to notice, though, that his medical school friends were much more excited about their work than he was. Then one night he had a revelation: If he became an English professor, his students would probably be relieved if he failed to show up for class. But if he became a doctor and canceled his appointments, his patients would be disappointed. He applied to med school.

Rejected by Harvard, Varmus ended up at Columbia. To avoid the Vietnam draft, he applied for and won a position as a “yellow beret” in the NIH’s Public Health Service. Once there, he gravitated toward the study of tumor viruses, partly because his mother had recently been diagnosed with breast cancer. Then, in 1970, he moved with his wife to San Francisco to work with Michael Bishop, a young microbiologist at UCSF. Their work showed that certain cancer-inducing viruses do their damage by capturing normal genes in the host’s own cells and turning them into cancer causers. This discovery led to the isolation of these so-called oncogenes.

“The research I did with Mike didn’t have the manic quality of some scientific discoveries, like the discovery of the double helix,” Varmus says. “This was Wagner rather than Mozart – a slow elaboration of themes, sung over and over again.” In the final act, Varmus and Bishop shared the 1989 Nobel Prize in Physiology or Medicine.

Varmus had always been passionate and outspoken, and with a Nobel in hand he found people more willing to listen. While continuing his research, he became increasingly involved in policy issues. In 1993, Donna Shalala, Bill Clinton’s secretary of health and human services, tapped Varmus to run the world’s largest biomedical research organization; as NIH director, he nearly doubled the agency’s budget, revamped its research programs, and hired some of the sharpest minds in science to run the individual institutes. Writing in The New Yorker in 1999, James Fallows wondered whether Varmus was “the most effective backstairs politician the Clinton Administration has produced.” The day before the 1998 State of the Union address, Varmus received an invitation just as he arrived in London on business. He responded that he would return to Washington if he could sit in the audience next to the First Lady. The next night, there he was at her side, the president beaming at them while announcing yet another increase in the NIH budget.

By this time, however, Varmus was growing restless. Too much of his schedule was occupied with administrative matters and answering to Congress.Though Varmus liked the feeling of being in charge, it was time to move on.

Then, in December 1998, Varmus met with one of Bishop’s former postdocs, a Stanford biochemist named Patrick Brown. Brown and a fellow of his, Michael Eisen, were using a technique for genetic analysis that benefits particularly from information-sharing across many labs. Eisen had written a program to enable such exchanges, but it was constantly banging up against copyright restrictions from journals that didn’t want the data in their articles passed around. Brown and Eisen thought that was insane. For a decade, the physics community had run an electronic archive out of Los Alamos National Laboratory, where researchers could upload their papers even before having them formally accepted by journals. The physicists loved it. Why not create something similar for the bio-medical community?

The conversation clicked with Varmus. Soon, he, Brown, Eisen, and David Lipman, an NIH colleague, drafted a proposal for “E-Biomed,” a public, one-stop repository of biomedical papers. Researchers could submit papers through a peer-review process similar to that used in the current journal system, or they could post work fresh out of the test tube.

In May 1999, seven months before leaving the NIH, Varmus published his vision for E-Biomed online with high hopes. It proved to be the first of several frustrating failures. There were hundreds of responses, some supportive but most antagonistic. Though the smaller, friendlier physics community had embraced the idea of freely sharing preprints, the more crowded and competitive world of biomedicine greeted it with open hostility, comparing it to socialism and lamenting what they saw as a loss of peer review. E-Biomed “is among the very worst ideas I have ever heard,” one University of Wisconsin-Madison biochemist told The New York Times.

Chastened, Varmus and his colleagues regrouped. Rather than challenge the journals directly, they would invite them to make their content available gratis in an online repository called PubMed Central after a six-month delay. The waiting period was a bitter pill for Varmus, but it would allow the journals to continue collecting revenue from subscribers who wanted the very latest research results. Still, only eight established journals accepted the invitation.

In the fall of 2000, the activists went on the offensive for a third time. They founded an organization called the Public Library of Science and circulated an open letter calling for the establishment of an online library that would provide the published record of biomedical research in a “freely accessible, fully searchable, interlinked form.” The signatories pledged not to publish in, edit or review for, or subscribe to any journal after September 2001 that did not make its content freely available in PubMed Central six months after publication.

Over the next year, 34,000 scientists signed the pledge. Journal editors decried what they rightly perceived as the threat of an economic boycott. And when September 2001 came around, most signers, fearing harm to their careers, backed away from their promise. The boycott crumbled.

Faced with this setback, Varmus and his coconspirators made their boldest move. If the journals were going to resist the open-access movement, then open access would take the battle onto the journals’ own turf: Varmus and his colleagues would become publishers.

In the UK, a spirited entrepreneur named Vitek Tracz had already started a venture called BioMed Central, publishing lower-level journals with revenue from authors’ fees. But Varmus wanted the PLoS journals to have the credentials to immediately draw outstanding submissions. They lured the editor of the top journal Cell to serve as executive director. They hired staff who had worked at both Nature and Science, and they began wooing prestigious contributors. “We felt we could make it work because we had revolutionary fervor,” Varmus says, “plus a $9 million grant from the Gordon and Betty Moore Foundation.”

PLoS quickly became a place for first-rate work. Recently, I asked a scientist whose work had appeared in a PLoS publication how much his choice of an open-access journal was based on support for this movement. “Open access?” he replied. “I just sent the manuscript to PLoS because I figured it was a good place to get published.”

And that’s the issue. Varmus is gratified that PLoS has established itself so quickly, but he’s frustrated at how slowly the scientific community is embracing his ideals. On the positive side, more scientists are sharing their work through listservs, preprint archives, and other informal networks that can be easily accessed through new searching and sorting tools like Google Scholar. On the other hand, the scientists at elite universities who can put the most pressure on the journals to change their policies have the least immediate incentive to do so, since they already have access to most of what they require through the subscriptions paid by their institutional libraries. Varmus also acknowledges that it’s easier for a scientist at his exalted level to call for career sacrifices, and things like boycotts, than it is for those still in the trenches to respond.

Behind Varmus’ office desk is a blowup of a photo taken 30 years ago of him paddling a raft down Wind River Country in Wyoming. He wears a fishing vest, his beard is bushy and wild, and he looks ecstatically happy. The picture was shot after his Nobel-worthy work with Michael Bishop appeared in Nature.

“I’d like to think that if I could do it over again, I would publish it in an open-access journal,” he says – adding, however, that he knows the thrill of appearing in the most prestigious journal. “The change will come when scientists understand that they are in control. The publishers need us more than we need them.”