Squeeze Play

Peter Grundy

Dorothea Fiedler has long been one to watch in the world of chemical biology. Her explorations of chemical language within cells ultimately could unlock new therapies for diabetes and obesity. The assistant professor attracted multiple grants to open her lab in the Department of Molecular Biology and seemed headed for tenure, but it never came to that. Last summer Princeton lost Fiedler after five years to a prestigious German research institute, the Leibniz-Institut für Molekulare Pharmakologie (FMP), which made her a full professor and director, with oversight over dozens of scientists. Most of Fiedler’s graduate students accompanied her to Berlin to finish their work, though they still will receive Princeton degrees.

Fiedler never felt funding constrained her path-breaking work, but believes it would have been impossible for Princeton to match what FMP was offering. “My job here [in Germany] comes with guaranteed funding for a certain number of co-workers, forever,” says Fiedler. “That means I can tackle real long-term projects, things that are challenging and may not work out, without having to worry about losing my grant.” Family reasons, too, figured in the German scientist’s decision.

Funding constraints are a big worry for scientists, young and old, at Princeton and across the country, especially those who rely on support from the National Institutes of Health. NIH funding stagnated over the past decade while the number of scientists seeking grants soared after Congress and the White House doubled spending on medical research between 1998 and 2003. Then, between 2003 and 2015, budget cuts and inflation meant that funding capacity plunged more than 20 percent, though Congress increased NIH spending in the 2016 budget. Today NIH supports fewer than one in eight requests for major funding; less than 40 years ago, the odds were two in five.

Princeton’s scientists have a much better batting average than most researchers — almost half the applications across the natural sciences and engineering departments were funded — but researchers here are not immune from the squeeze. Almost 85 percent of the $200 million in sponsored research on campus each year is funded by Washington, principally NIH and the National Science Foundation (NSF). Separately, the U.S. Department of Energy underwrites nearly the entire $100 million budget of the Princeton Plasma Physics Laboratory on Route 1.

“It’s almost a crapshoot,” says Thomas Silhavy, a renowned bacterial geneticist who has had two NIH grants for decades. Today his lab, with seven people, is smaller than it has ever been, he says. “But I’m lucky. I’m still surviving. If you lose your grant and have to close your lab, it’s over. It’s never, ever going to come back.”

“My job here [in Germany] comes with guaranteed funding for a certain number of co-workers, forever.”
— Former Princeton professor Dorothea Fiedler

Sameer A. Khan

“We’re like these little entrepreneurs. I can only have as many people in my lab as I have grant money to pay them.”
— Professor Bonnie Bassler

Zach Donnell

As part of the University-wide strategic planning effort that President Eisgruber ’83 launched soon after taking office in 2013, two high-powered task forces recently made recommendations for the future of the Graduate School and for sponsored research at Princeton (see PAW, March 16, 2016). They urged University trustees to marshal millions of dollars in new resources to expand the Graduate School, provide more support for graduate students who are the lifeblood of research labs, and create new, internal innovation funds for young and mid-career researchers to buffer them from the vagaries of federal funding and encourage them to pursue novel, even “crazy” ideas (in the terminology of Dean for Research Pablo Debenedetti) that might not pass muster with NIH selection panels looking for assured results.

Princeton’s Graduate School is unusual among the ranks of top U.S. research universities against which it competes for faculty and students. It is far smaller than most, and 90 percent of the 2,700 graduate students are pursuing Ph.D.s, not master’s or professional degrees. Princeton’s toughest competition for students comes from Harvard, MIT, Stanford, and the University of California, Berkeley, according to the task force on the Graduate School. That competition begins with how much support these institutions promise upfront to Ph.D. students — and Princeton’s rivals are not standing still. Stanford, for example, recently announced a $400 million gift from alumnus and Nike founder Philip Knight toward a $750 million endowment to provide 100 more fellowships to its graduate and professional schools.

Princeton funds Ph.D. students fully through a combination of fellowships, research assistantships, and teaching assistantships (students in science and engineering receive $30,000 stipends). A typical $200,000-a-year NIH grant “covers two graduate students and their supplies,” says Bonnie Bassler, the chair of molecular biology. Her department has at times not accepted all the graduate student slots it was allotted due to uncertainty over whether it could place them all in labs after their first year of studies.

Apart from a professor’s paycheck during the academic year and the core facilities the University provides, “everything else you do — your grad students, postdocs, every reagent, every piece of equipment you buy, your summer salary — all of that is bought on these grants. We’re like these little entrepreneurs. I can only have as many people in my lab as I have grant money to pay them,” says Bassler. “Graduate students are the engine that drives science. We love them. But we won’t take more unless we know we can afford them.”

Bassler’s lab is one of Princeton’s best-funded. Her team focuses on the molecular mechanisms that bacteria use for intercellular communication, work that could lead to improved antibiotics and new anti-microbial drugs. She currently has two NIH grants, two National Science Foundation grants, and is one of Princeton’s three Howard Hughes Medical Institute investigators, a coveted status that pays her salary and more (Shirley Tilghman was an HHMI investigator before becoming president). “The molbio faculty is spectacular. Great people want to come and work here,” Bassler says. “But when funding gets scarce, there’s a tendency to circle the wagons. Now when you send a grant in, you don’t put in your most imaginative idea. You start thinking smaller. That is not how you innovate. I don’t want Princeton’s faculty or students doing that kind of science.”

Debenedetti, too, is concerned that given the paralysis in Washington, the temptation even for faculty the caliber of Princeton’s is to “propose incremental but safe things. They write about the research they already did, not what they want to do.” The task force on sponsored research, chaired by Debenedetti and Provost David Lee *99, suggested that Washington prefers such “safe” proposals because they’re viewed as more likely to produce the sought-after results.

That task force exhorted Nassau Hall to find the resources to blunt the downward trends in federal support for R&D. It recommended creating four-year, $150,000-per-year innovation awards for young and mid-career faculty to pursue new avenues of research and to tide professors over between outside grants. Faculty also could compete for $50,000 grants to prepare proposals and get $75,000 matching grants when they snare federal or industrial awards. The cost to Princeton: $7.4 million. The panel also recommended that the University create a $5.4 million fund to pick up the share of tuition of fourth- and fifth-year students that is now charged against research contracts. (In a separate report, the Graduate School task force urged more support for humanities and social-science doctoral students in the sixth year. While scientists and engineers typically graduate in five years, it takes 6.2 years on average to earn a Ph.D. in the social sciences and 6.7 years in the humanities.)

Debenedetti framed the research-funding challenge not as a crisis but a unique opportunity to build on Princeton’s strengths. “I don’t want to paint the image that the sky is falling,” he says. “There’s considerable cause for concern, but we have a fantastic faculty who are competing extremely well.”

When biologist Danelle Devenport, then a postdoctoral fellow at Rockefeller University, was flying around the country for job interviews, she was taken aback by something she kept hearing in heart-to-heart conversations with senior scientists. “It went like, ‘You kids are crazy to do this. It’s so much harder these days to keep your lab funded and keep students and postdocs in the lab,’” she recalls. “I heard that in every place. Some seemed more downtrodden and depressed.”

But at Princeton, “nobody gave me that speech,” says Devenport, an assistant professor since 2011. Proffered along with the job offer was $1 million to start up her lab, enlist doctoral students and postdocs, and begin experiments on how cells assemble to produce functional organs. Soon she attracted large federal and foundation grants for promising young investigators, and in 2014 landed her first big NIH grant, the kind for which every biomedical researcher in the country competes.

Devenport appears on the verge of snagging a second NIH grant, but the application process is torturously slow. From start to finish it took two years for the first grant to come through. The anonymous peer reviewers demanded “a lot of preliminary data to show everything you propose is actually feasible. Logically that makes sense, but it’s very hard to predict the future in science. There’s an element of luck,” says Devenport, whose team studies cells in vivo (mouse skins) and in vitro (petri dishes). She adds: “My students tell me, ‘I’m not sure I want your life. Your life is crazy.’ They see the door closed when I’m writing grant submissions. Writing grants is something that no graduate student looks at and says, ‘Yeah, that’s what I want to do.’ ”

Clifford Brangwynne, an assistant professor in chemical and biological engineering, attests to how slow-moving the grant-approval machinery moves in Washington, although he, too, has snagged young-investigator grants from both NIH and NSF and a big NIH grant for his work on phase transitions in cells. His team has made discoveries that ultimately could have implications for treating neurodegenerative diseases such as Lou Gehrig’s and Alzheimer’s — but that wasn’t evident when he began. Brangwynne, whose fifth-grade daughter recently had an assignment on the Lewis and Clark expedition, stressed the importance of pursuing the unknown, as the explorers risked their lives doing. “You don’t know what you’re going to find out there at the frontier, but that’s where the good stuff is,” he says.

This isn’t Princeton’s first push to buffer its own explorers from the vicissitudes of budget battles and woes in Washington. In 2013, the University created an innovation-awards competition that offers grants of up to $250,000 for faculty with bold ideas; the dean for research funded 15 projects, including two in the humanities, in the first two years. In addition, in 2009, Eric Schmidt ’76, the executive chairman of Google parent Alphabet Inc., and his wife, Wendy, endowed a $25 million fund to support risky yet potentially groundbreaking faculty research. It funds projects just off the drawing board that are far too new to produce the preliminary results upon which federal funders insist. (Two smaller grant programs — the Project X Fund and the Intellectual Property Accelerator Fund — have similar goals.)

Gerard Wysocki, an assistant professor of electrical engineering, and Daniel Sigman, professor of geosciences, received $700,000 from the Schmidt fund in 2012 to develop a sophisticated, portable instrument to measure nitrogen isotopes and monitor environmental change. They succeeded — and now Sigman can take the equipment with him as he studies oceans’ response to climate change going back to the ice ages. Asked if they could have persuaded the National Science Foundation to fund the project at the outset, Wysocki says, “Absolutely not. We didn’t have the instrument yet to show results. Now we do.”

Elise Piazza, a postdoc who joined the Princeton Neuroscience Institute last fall after completing her Ph.D. at the University of California, Berkeley, quickly enlisted three more senior colleagues and won a $577,000 Schmidt award to develop a new imaging system to study what happens inside the brains of infants as they learn language. Instead of subjecting babies to the clamor of magnetic resonance imaging (fMRI) machines, the researchers will beam low-intensity light through unobtrusive caps worn by babies and caregivers to measure neural activity and possibly shed light on autism. “Many national grants don’t encourage super-risky, groundbreaking research,” says Piazza, who will be the principal investigator in the PNI Baby Lab project. “They like to first see really strong evidence that something’s going to work. This involves a lot of unknowns.”

Some faculty “propose incremental but safe things. They write about the research they already did, not what they want to do.”
— Dean for Research Pablo Debenedetti

Frank Wojciechowski

“It becomes harder to accept a very promising student who may not fit exactly into [a given] project.”
— Professor Daniel Sigman

Denise Applewhite/Offfice of Communications

Biochemist Sabine Petry, an assistant professor, leads an interdisciplinary project that received $723,000 from the Schmidt fund to develop a microscope that will allow researchers to manipulate chromosomes while viewing in 3-D the interior of a living cell. She teamed with two tenured professors, chemistry professor Haw Yang and physicist Joshua Shaevitz. “There’s no way we could have gotten any kind of traditional funding from the NIH,” says Petry. “It’s a super-ambitious idea ... and a research direction that we would not have picked up working alone.”

Petry runs one of four dozen labs in the Department of Molecular Biology, a crown jewel of Princeton’s scientific enterprise and one that has been hit hard by the funding crunch. The pressures there, the research task force said, “are especially urgent.” From its founding in 1984, molbio has focused “on discovery, the front end of the pipeline” for new medicines, says former department chair Lynn Enquist. “You can’t translate anything into medicine if you don’t have new ideas. By definition, a discovery means you don’t know what you’re looking for until you find it.” Enquist was chair during the Great Recession, when Princeton cut spending across the board by 5 percent. The department marshaled resources to provide bridge funding to faculty whose NIH grants lapsed, “and I made a commitment to the graduate students that if a lab went belly up, we wouldn’t kick them out,” he says.

Science graduate students in departments across the University “shop” for labs by doing three rotations during the first year while taking classes. Many gravitate to labs that need specific computational or other skills, “but you’re also looking for someone with great intellectual potential,” says geoscientist Sigman. “You don’t want to choose someone simply for the role they can play in a given research project,” he says. Still, when funding gets tight, “it becomes harder to accept a very promising student who may not fit exactly into that project. That’s not good for the U.S. in terms of developing new scientists.” Some professors elect to hire a postdoc — who comes for a year, often with outside funding — rather than make a three-year commitment to a Ph.D. student.

The difficulties of securing funding are changing how some graduate students think about careers in academe, which could affect which research gets done — and where — in the future. While most humanities Ph.D.s compete for a limited number of academic openings, newly minted science and engineering Ph.D.s have many attractive choices. Molecular biology tracked the 208 students who earned doctorates from 2005 to 2015 and found that 97 percent had landed positions — 36 percent in industry, 34 percent in postdoctoral positions, 11 percent as faculty, 11 percent as consultants or in the financial industry, and 5 percent in medical school.

Astrophysicist Hantao Ji says that in physics, “We’re fighting for the best students, fighting against financial engineering and mechanical and biological engineering. Good students see those fields are growing and a lot of jobs out there. It’s harder and harder to convince them to commit to careers in academe and basic research.” But astrophysicist David Spergel ’82, who plays a key role in NASA’s multibillion-dollar push to build a successor to the Hubble Space Telescope, notes that doctoral students always have had choices outside academe. “When I was a student, a bunch of people went off to work on defense things,” he says. “Nowadays, if they leave the field, they tend to go into finance or go work for Google.”

Francine Camacho, a second-year Ph.D. student at the Lewis-Sigler Institute for Integrative Genomics, came to Princeton seeing her future in academe. But witnessing what she calls “the academic Hunger Games” now has her leaning toward the pharmaceutical or technology industry. “I’ve seen graduate students doing four, five, or even six rotations because labs are not taking graduate students since they can’t financially support them,” Camacho said. Akshay Mehra, in geosciences, says the department works hard to get larger grants so it can provide generously for its students. But as an officer of the Graduate Student Government, he’s heard “from one or two people who’ve struggled to convince their adviser to spend money on their research.”

“I’m an eternal optimist,” says neuroscience grad student Laura Bustamante, who still dreams of opening a lab of her own one day. “You have to have a superstar résumé and get published in the best journals. Ultimately, some talented researchers [won’t be] able to land a faculty job or get funding, but they’ll receive great jobs somewhere else. A Ph.D. can take you a long way in a bunch of different directions.”

No one is sanguine that Washington will open the spigots for basic research anytime soon, as it did after World War II and Sputnik and into the 1980s. “Even if there is bipartisan appreciation in Washington for the value of research and education in the abstract, strains on discretionary spending and political battles over the budget will almost certainly limit government funding for sponsored research in the years ahead,” the trustees said in a strategic-planning framework released in January.

But neither is anyone expecting the spigots to be turned off completely. The task force on sponsored research assumed that government funding will remain “the backbone of Princeton’s research enterprise.” It did not suggest retrenchment or curtailing any area of research, but it did look at what would happen in a “worst-case scenario,” which it defined as an 8 percent cut in federal support. It canvassed four departments — molbio, astrophysics, mechanical and aerospace engineering, and physics — and each indicated that in such a hypothetical situation they would keep their faculty and graduate students while trimming the number of postdocs and lab staff. “Young people are sacred in this department,” Bassler says.

By and large, lawmakers on both sides of the aisle support scientific research (although House Republicans last year unsuccessfully sought to cut NSF funds for climate-change research). “It’s not that we have enemies in Congress, but when the budget is tight and everyone gets cut, we get cut as well,” says Spergel, the astrophysicist.

Still, it’s always good to have a Plan B, some suggest. Ask Ethan Perlstein. He earned his Ph.D. in molecular and cell biology at Harvard, then completed five years of postdoctoral work in genomics at the Lewis-Sigler Institute. After applying for 18 tenure-track positions and getting not a single interview, he gave up in 2012 — and then used Twitter and other social media to find angel investors to open his own lab in San Francisco. He raised $2.5 million and now works with four other scientists to find marketable, so-called orphan drugs to treat rare childhood diseases. He calls himself an “indie scientist” and thinks others would be wise to follow his example.

“People have to build their own networks and take control of their lives,” says Perlstein. “Planning around what’s going to happen with NIH and thinking there’ll be a turnaround if we just wait out this storm, that’s a fool’s errand.” 

Christopher Connell ’71 is a journalist in Washington, D.C.