Nobelist Randy Schekman Is Not Resting on His Laurels

By Katia Savchuk

When Randy Schekman looks up from his computer screen, which he now spends more time staring at than petri dishes, his eyes sometimes fall on a faded copy of Cell displayed nearby. The issue is dated June 17, 1994, and the cover depicts a swarm of magnified vesicles—tiny sacs that transport molecules inside cells—resembling a crowd of miniature suns.

Inside the journal, Schekman and his collaborators laid out one of his lab’s most important findings. They identified certain proteins needed to form vesicles, by re-creating the process in a test tube. It was one of a slew of discoveries about how cells shuttle particles. Many of the findings were reported in journals such as Cell, Science, and Nature, and in 2013 resulted in Schekman’s sharing the Nobel Prize in Physiology or Medicine.

Schekman, now 67, has spent the last 40 years as a professor of molecular and cell biology at UC Berkeley. He isn’t resting on his laurels. He’s used his newfound influence to speak loudly, wherever he can, about everything that’s wrong with scientific publishing and public higher education in the United States. He’s written editorials, made speeches, given radio and television interviews, and hosted chats on Reddit and Twitter. The most frequent targets of his attacks: Cell, Science, and Nature. The day before he picked up his Nobel in Stockholm, Schekman announced in The Guardian that his lab would boycott what he called the “luxury journals,” singling out the Big Three. Now, as editor in chief of eLife, a three-year-old open-access scientific journal, he expressly aims to change the way these elite publications and others do business, if not put them out of it.

The seeming hypocrisy is not lost on Schekman. On a recent Monday morning, between a conference call with eLife’s staff and a meeting with scientists in his lab, he recalled the barbs he’d read on blogs or heard through colleagues: “Yeah, Schekman can say this, he’s got his Nobel Prize. But what about me? I have to play the game.” Or “He published in those journals all along as he was coming up!”

Schekman, who is small of stature with wire-rimmed glasses and a bushy red mustache that’s fading to gray, shrugs off the criticism. “I have a pretty thick skin,” he says, laughing. “I made those statements after receiving the prize, precisely because I had a soapbox. I’ve been saying stuff like this all along, but who would listen?”

Following his lead may be easier said than done for young researchers. “As long as allocation of funding and positions depends on the lazy analysis of where applicants have published rather than what they have published, then many young scientists will be dissuaded from joining this or future boycotts,” wrote Thomas Livermore, a doctoral student at University College London, in a response to Schekman’s Guardian piece.

The Nobelist acknowledges the bind young researchers like Livermore are in. He calls it “part of the cultural problem that we’re up against.”

Schekman first noticed that scientific publishing was going off the rails in the early 2000s, when he was senior editor at The Journal of Cell Biology. He says Ira Mellman, then the editor in chief, told him the journal should reject more papers. The directive had nothing to do with research quality or limited space—it was simply to boost the journal’s “impact factor.”

That metric was the brainchild of Eugene Garfield, a linguist and library scientist, who devised it in the 1960s to select journals for his new index of scientific citations. Impact factor was a proxy for quality, capturing the average number of citations per paper published in a given journal over the previous two years. (Garfield’s work inspired Sergey Brin and Larry Page as they developed Google’s search algorithm.) Later, librarians used it to pick journal subscriptions. Then the impact factor took on a life of its own, especially after Garfield sold his Institute for Scientific Information, which published the index, to the Thomson Corporation (now Thomson Reuters) in 1992. Eventually, scientific journals started altering their publication strategies—preferring articles on trendy topics, restricting acceptance rates—to beef up their impact factors. Some universities and funders began basing decisions about hiring, promotion, and grants on the figure.

All of which rankled Schekman. “This phony number became a metric for scholarship, which is ridiculous,” he says. “I felt this was doing damage to scholarship. People were no longer concerned with what was in the paper—they were just concerned about where it was published.”

The rise of the impact factor paralleled the tightening grip of large commercial publishers on scientific output. In 2013, the five biggest publishers put out more than half of all scientific papers. In 1973, when Schekman was in graduate school, those publishers accounted for only 20 percent. As the commercial giants gobbled up existing journals and created new ones, they reaped billions of dollars in revenues and profit margins above 30 percent. Control shifted from working scientists to professional editors.

When Schekman took over as editor in chief of the Proceedings of the National Academy of Sciences (PNAS) in 2006, he banned discussion of the impact factor. He told the board and staff, “We’re going to measure scholarship by our own scientific criteria, and we’re not going to change what we publish to generate more buzz.” Most were happy to comply, but marketing staff urged him to pump up the number.

After his five-year term, Schekman evaluated the journal’s progress for the National Academy of Sciences Council. A member he admired called him and said, “This is a great report, but how’s the impact factor doing?” He blew up: “This is ridiculous—I don’t care what it is!”

After his five-year term, Schekman evaluated the journal’s progress for the National Academy of Sciences Council. A member he admired called him and said, “This is a great report, but how’s the impact factor doing?” He blew up: “This is ridiculous—I don’t care what it is!”

There was another glaring problem with PNAS’s publishing model. Members of the Academy could publish up to four papers a year that had a single review from a handpicked colleague. Schekman says the policy had been abused, and he encouraged the journal’s editors to apply more scrutiny to members’ papers and reject them if warranted.

Still, he appreciated that active scientists, as opposed to professional editors, ran PNAS, and he planned to sign on for another term. Before he did, though, his colleague of 30 years, Robert Tjian, came to him in 2011 with an opportunity Schekman couldn’t resist. Three mammoth private funders of biomedical research—the Wellcome Trust, the Max Planck Society, and the Howard Hughes Medical Institute (which Tjian led)—were starting a new nonprofit journal and wanted Schekman as editor in chief. They’d committed around $29 million for five years. This was Schekman’s chance to create a new model for scientific publishing.

In December 2012, eLife launched as an online journal for life sciences and biomedicine. Besides making content freely available, as the Public Library of Science (PLoS) and others had been doing for nearly a decade, Schekman wanted to reimagine the review process. He staffed the editorial ranks with prominent working scientists. Instead of a protracted evaluation process, he vowed to decide within days whether a paper would be reviewed and to limit revisions to one round in most cases. In 2015, the median time between submission and acceptance at eLife was less than four months, compared with a review process that can last more than a year at top-tier journals.

Most importantly, peer review would be consultative. Rather than scientists working anonymously to produce separate, often disparate, evaluations, eLife reviewers would confer with each other and the editor to compile a single review. They could request no more than two diverging experiments. At commercial journals, reviewers can bog down researchers with dozens of conflicting experiments, or even request tests they know are impossible to run, in order to prevent publication. “This happens all the time. It’s a very competitive field,” Tjian says.

Schekman spends more than half his time running eLife, based in Cambridge, England, from his office on the sixth floor of Cal’s Li Ka Shing Center for Biomedical and Health Sciences. Now in its fourth year, the journal has published 1,700 papers, and submissions have exploded to 700 a month.

One reason for its rising popularity is the very thing Schekman has vowed to ignore: impact factor. Despite Schekman’s request that eLife be removed from the rankings, Thomson Reuters still includes it—along with its impact factor, which has risen to 8.3, far below Cell (28.7) or Nature (38.1), but still in the top 3 percent of all 8,000 journals ranked. Schekman acknowledges the irony but says only, “I don’t look, and I don’t care.”

No story of a Nobel laureate is complete without recounting “the call.” For Schekman, it came at 1:20 a.m. on October 7, 2013. Someone with a “nice, reassuring Swedish accent” told him he’d share that year’s Nobel Prize for Physiology or Medicine with two biochemists: James Rothman at Yale and Thomas Südhof from Stanford. Schekman had been a likely candidate for decades, but now he couldn’t stop saying, “Oh my God.” He danced around with his wife and called family and friends. Later that day, his students donned fake mustaches and popped champagne to celebrate, and Cal honored him with the customary lifetime parking permit.

Schekman quickly realized that the prize gave him a new pulpit from which to address his mounting concerns—not just about scientific publishing, but also about decreased funding for public colleges and universities. “I realized this was an opportunity to say something louder than I’ve said in the past,” he recalls. “I’m not going to become a politician or change the course of biomedical funding in this country, but I think we can make a change here.”

In his first official talk as a laureate, to the National Institutes of Health that November, he railed against the harmful effects of the impact factor, pointing out that the Chinese government was offering rewards of $33,000 to scientists who published in Cell, Nature, or Science. (“I was insulted to learn that a PNAS paper was only worth about $5,000,” he joked.) He urged the crowd to join him in signing the San Francisco Declaration on Research Assessment, an initiative to improve evaluation of scientific research, which has gathered more than 12,400 individual signatures since 2012.

Schekman timed his most forceful remarks to coincide with the Nobel awards ceremony that December. The day before he appeared in coattails before the Swedish king, he editorialized in The Guardian against the “tyranny of the luxury journals,” comparing it with the “hold of the bonus culture” on Wall Street, which “drives risk-taking that is rational for individuals but damaging to the financial system.”

He called for others to join his boycott of Cell, Science, and Nature. The next morning, he debated an editor from Science on a BBC radio program. In press reports, editors of the journals denied that impact factor drove their editorial decisions, and touted their quality and review processes.

Unlike some advocates of open access, including his outspoken Berkeley colleague Michael Eisen, a cofounder of PLoS, Schekman started out being skeptical of the new model. In 2007, when he was editing PNAS, he told the Berkeleyan that he hadn’t signed PLoS’s manifesto that all scientific papers immediately become freely available, because “having been an editor for the Journal of Cell Biology for many years, I realized that this would be the death of many of the journals—even those run by some of the scientific societies.”

Schekman’s thinking evolved after he observed the success of PLoS journals, which charge authors a fee of up to $2,900 per published manuscript. In 2011, he called for a federal policy mandating that all publishers of life sciences research make content freely available within six months. “For journals that must break even or generate a little profit, a limited embargo is a reasonable compromise,” he says today.

Eisen, who goes further than Schekman to argue that peer review and traditional journals are obsolete, nevertheless commended the elder scientist on his blog after the Nobel announcements. “I know that most people will dismiss Randy’s example, because they have done it to me. This is sad…. We need more than a handful of Nobel Prize winners and true believers to abandon the current system. So what’s it going to take?”

Schekman, who spent all but four years of his academic life in the UC system, has been equally vocal about declines in state funding for public higher education. He raised the issue when addressing the UC Regents after his Nobel win, in a televised BBC roundtable discussion with the 2013 laureates, and again during his UCLA commencement address in 2014. (Basketball player Kareem Abdul-Jabbar, Schekman’s former classmate, introduced him at that event—an honor the Nobelist said topped meeting the Swedish monarch. As an undergrad, Schekman attended all of Abdul-Jabbar’s home games, when the star center was still known as Lew Alcindor, and keeps a framed photo of him on the wall behind his desk.)

Schekman frequently points out that he paid just $40 in fees and $400 for room and board per semester as an undergrad at UCLA, expenses he could fund with a summer job. The current cost to attend a UC, including room and board, is upwards of $25,000 per year for in-state students, though it varies by campus. “Public education was considered an investment in the future, and now it’s considered a private commodity that is the largest source of debt in this country,” he says.

In December 2013, Schekman published an op-ed in the San Francisco Chronicle, noting that he was the only one of 11 laureates that year hailing from an American public institution, and calling for more funding. Schekman has personally persuaded wealthy donors to contribute to UC schools and accompanied UC President Janet Napolitano to lobby Democrats in the state legislature, as well as Governor Jerry Brown ’61. (Brown sent one of his staff members in his place to their lunch meeting, which the biologist considered “a direct rebuff.”) He even donated his Nobel Prize money to Berkeley to create an endowed faculty position in honor of his mother and sister, who both died of cancer.

Schekman grew up in a tract home near Long Beach, the eldest of five children. His father was a computer engineer and his mother was a homemaker. All the kids attended public school.

His passion for microbiology started with pond scum. When he was 10, he used a toy microscope to examine a sample from a local creek. “I saw this world come alive, and I just couldn’t believe it. I was endlessly fascinated,” Schekman recalls.

“For me it was like reading passages from the Bible,” Schekman says of discovering James Watson’s Molecular Biology of the Gene. “It was a revelation.”

He babysat, mowed lawns, and delivered papers to save up $100 for a student microscope, but his mom had a habit of dipping into this savings for groceries. Furious, he biked to a police station and announced he was running away from home because his mother was stealing his money. When his father picked him up, they drove straight to a pawnshop to buy a microscope. In high school, Schekman grew bacteria in petri dishes in his room, feeding them with outdated blood he got from a local hospital.

When he enrolled at UCLA, Schekman planned to become a doctor. That changed during his freshman year, when he studied with Willard Libby, a Nobel laureate who had invented radiocarbon dating. After ten weeks in a lab, Schekman was set on becoming a scholar. The same year, his lab supervisor handed him a copy of Molecular Biology of the Gene, the first edition of James Watson’s textbook. “For me it was like reading passages from the Bible. It was a revelation,” he remembers.

In 1970, he enrolled in Stanford’s ultraselective biochemistry program to work in the lab of Arthur Kornberg, another Nobel laureate. From Kornberg he learned how to take a scientific problem apart piece by piece, but the two also clashed. “He could be pretty brutal. He was there to make sure the best science got done and didn’t necessarily care how many egos or emotions were stepped on. I’m stubborn and did things my own way, and I probably mouthed off at him too often,” Schekman says.

Bill Wickner, who joined Kornberg’s lab in 1971, grew to be Schekman’s best friend. Wickner advised him to avoid the draft by going on an all-coffee diet to raise his blood pressure. He also introduced Schekman to Nancy Walls, a nurse Wickner had once dated. After their first meeting, Schekman hugged his friend and said, “That’s the girl of my dreams.” They married two years later and eventually had a son and daughter.

After two years of postdoctoral work at UC San Diego, Schekman joined Cal’s faculty in 1976. His first breakthrough came two years later. His lab isolated a genetic mutant that blocked secretion in yeast cells and they examined it through electron microscopy. The resulting image of brown cells that appeared to have the measles is still tacked up near his desk. When Schekman first saw the image, he knew the discovery would open the door to decades of study. His lab went on to isolate many other mutants affecting the transportation system of cells. In 1985, his graduate student David Baker re-created part of the cell’s process in a test tube, initiating years of biochemical breakthroughs.

Schekman became known as an energetic and candid leader, and many of his students emerged as prominent scientists in their own right. “Randy will tell you what he thinks. He can be very supportive, but also very critical. Some people found that kind of tough, but I think in the end it’s what you need,” says David Julius, a former student of Schekman’s who chairs the physiology department at UCSF.

“Randy will tell you what he thinks. He can be very supportive, but also very critical,” says former student David Julius. “Some people found that kind of tough, but I think in the end it’s what you need.”

Although Schekman’s goal was to understand how living cells work, not to cure diseases, his landmark discoveries have had wide applications. When the transportation systems of cells break down in humans, it can contribute to neurological diseases, immune system disorders, and diabetes. That aspect of his research became personal when Schekman’s wife, Nancy, at age 48 was diagnosed with Parkinson’s disease, which eventually led to dementia.

Whether Schekman’s advocacy has been as effective as his science is hard to say, but it has been making inroads. And eLife’s funders committed another $36 million to bankroll the journal through 2021. Its rising number of submissions—and even its impact factor—suggest the model is working. Some publications, including The Plant Cell and eNeuro, have adopted the consultative review process, and others are experimenting with it.

In July, executives from major scientific publishers, including Springer Nature, the owner of Nature, put out a draft paper proposing that journals use a metric showing the range of citations their articles receive, in order to counter misuse of the impact factor. The same month, the American Society for Microbiology published an editorial in eight of its publications, declaring it would no longer publicize the impact factors of its journals.

“I think our critics are coming around,” Schekman predicts. “Although the commercial journals probably aren’t suffering yet, I think they feel us breathing down their necks.”

When it comes to public education, Schekman says he feels more powerless. He plans to continue fundraising and bringing up the issue to whoever will listen, but he doubts state officials will turn things around anytime soon.

Not far from the copy of Cell is displayed a blown-up still from the film It’s a Wonderful Life, which Schekman has watched every year since he was a kid. His colleagues gave him the photo when he stepped down as department chair. Gazing at the image, he reflects, “I began to see this place as the Building and Loan in Bedford Falls, always on the verge of bankruptcy and being overtaken by the evil Mr. Potter. In my rich fantasy life, I’ve always thought of myself as Jimmy Stewart.” 

Katia Savchuk is a reporter for Forbes.

From the Fall 2016 The Greatest Show On Earth issue of California.
Filed under: Science + Health
Image source: Marcus Hanschke
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