How Pew’s Biomedical Scholars Drive Cutting-Edge Science to New Heights

  • May 11, 2016
  • by Karen Hopkin

© Katye Martens / The Pew Charitable Trusts

Scholarships often come at a critical time for promising young scientists. Pew biomedical scholars Patricia Ducy, Qing Fan, and Ivaylo Ivanov are researchers at the Columbia University Mailman School of Public Health in New York City, and Ducy says the Pew grant "basically opened my career."

It was at the 1997 annual meeting of the Pew biomedical scholars in Puerto Vallarta, Mexico, that newly minted scholar Greg Hannon first heard Craig Mello (class of 1995) talk about a phenomenon called RNA interference, or RNAi, in which small RNA molecules could be used to block the activity of specific genes, allowing study of their function.

“It sounded like this magical thing: Tiny bits of RNA could silence genes throughout a worm’s body—even across generations. But Craig said he didn’t know how it worked,” recalls Hannon, currently at Cancer Research UK Cambridge Institute. “I was intrigued, so I spent some time talking to him about it.”

“He peppered me with questions,” laughs Mello, who now runs a laboratory at the University of Massachusetts in Worcester. And Hannon wasn’t the only one. Richard Carthew of Northwestern University (Pew biomedical scholars class of 1995) was similarly “charged up about RNAi,” Mello says. “I distinctly remember Rich asking, ‘Do you think it will work in flies?’ And me saying, ‘Well, probably not’—although I did urge him to try it.”

“At the next meeting, Rich got up and announced that he’d tried RNAi in fly embryos and it worked,” says Hannon. “I left and called my lab and said, ‘OK, here’s what we’ll be working on now.’” The Pew Scholars Program in the Biomedical Sciences, he says, “completely changed the trajectory of everything I did.”

In its way, RNAi has changed the trajectory of modern molecular biology. The approach gave researchers unprecedented access to the innermost workings of living organisms, providing a powerful experimental tool for unraveling the role that each and every gene plays in most fundamental biological processes. At the same time, RNAi holds the potential to study and even treat human diseases, many of which are caused by the activation of genes at the wrong time or in the wrong place.

Along with Mello, who took a genetic approach, Hannon, Carthew, and Phillip Zamore (a 2000 scholar also at UMass in Worcester) helped to dissect the molecular mechanisms that govern the process. “So many of the really important people in the field were [Pew biomedical] scholars,” says Mello, who went on to share the 2006 Nobel Prize in physiology or medicine with his collaborator, Stanford University’s Andrew Fire, for the work he started as a scholar. “RNAi really owes a lot to Pew.”

So do many of the scientists who can trace their success in part to their experiences as Pew scholars. Since its beginnings, the Pew scholars program has provided funding to more than 600 outstanding young researchers whose work seeks to improve human health. More importantly, the program has fostered countless collaborations and informal intellectual interactions among this cohort of curious and creative academicians—like the work surrounding the study of RNAi.

“It was created to be a program that funded the best of science, and all about data and research—two words that underpin everything we do at Pew,” says Rebecca Rimel, president and CEO of The Pew Charitable Trusts, who helped establish the scholars program three decades ago, not long after joining the organization as a manager of health programs. And while the Trusts were created nearly 70 years ago, the biomedical scholars program was the first to carry the Pew name. 

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Pew biomedical scholar Roderick MacKinnon won the Nobel Prize for chemistry in 2003.

Each year, more than 180 academic institutions across the country are invited to submit a single nominee for consideration, and since 2014, program alumni have been invited to do the same. The nominees’ applications are reviewed by the national advisory committee, whose members—led by Mello, the current chair—select 22 scholars to receive support for four years. The award is meant to “foster innovation and risk-taking, encouraging scientists to take their work in new and uncharted directions,” says Rimel.

For George O’Toole of the Geisel School of Medicine at Dartmouth (class of 2000), the funding allowed him to study how bacteria form biofilms in the airways of patients with cystic fibrosis. Exploring how microbes interact in a host tissue, O’Toole says, “has allowed us to ask questions other people haven’t been able to tackle, and has become a big part of what we do in the lab.”

Because it rewards innovation, the scholars program gives researchers the freedom to pursue ideas outside the mainstream, says Columbia University’s Patricia Ducy (class of 2001). “No one would have funded my crazy idea,” she laughs. “We had zero data. But we had a gut feeling.” That intuition led to the discovery that cells in the bone can regulate the secretion of insulin—work that could open up a new approach for combatting diabetes. Because she had no support from other sources, Ducy notes, the grant from Pew “basically opened up my career.”

Funding risky ideas is “one of the most valuable aspects of the program,” notes Yale University’s Nancy Carrasco (class of 1989). Her challenging project involved cloning the transporter protein that allows cells to take up iodide, which the body uses to produce thyroid hormones. She has since thoroughly characterized the operation of the transporter and discovered that the protein is present in breast cancers, a finding that could lead to a new approach to treating the disease.

Pew’s backing similarly allowed Victor Velculescu of Johns Hopkins University (class of 2004) to undertake a novel large-scale genetic analysis that turned up PIK3CA, a gene involved in cell proliferation and survival that he says “is one of the most frequently mutated genes in human cancer.” That discovery is leading to more personalized treatments that take into account the specific genetic derangements present in the tumors of each individual patient.  

One reason that scholars feel empowered to pursue such “high-risk, high-reward” lines of research is that the program supports a person, not a project. “When launching the program, we felt strongly that investment in individuals pays huge dividends,” says Rimel.

The scholarship also comes at a critical juncture, when researchers are trying to establish their young careers. Felicia Goodrum of the University of Arizona (class of 2008) used her Pew funding to develop an animal model in which she could study cytomegalovirus, a virus—related to the ones that cause chickenpox and mononucleosis—that infects only humans. By generating mice with human bone marrow, Goodrum could identify the viral genes that allow this infection to persist in people with a normally functioning immune system. “Pew gave me the confidence that we could make this work,” says Goodrum. “They believed in the project and in me.”

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Pew biomedical scholar Craig Mello won the Nobel Prize for physiology or medicine in 2006.

In addition to a vote of confidence and financial support, the program sponsors an annual meeting that brings the scholars together to get their creative juices flowing. At these gatherings, the scholars discuss their work and exchange ideas. And because they come from a variety of fields, the scholars hear about science that is outside their area of expertise, leading to conversations that can spark new ideas and innovative collaborations.

At a recent Pew reunion meeting, Andrew Ellington of the University of Texas at Austin (class of 1994) was inspired by a talk given by 2007 scholar Julie Pfeiffer of the University of Texas Southwestern. She discussed how the bacteria that live within an organism—its microbiome—might inadvertently act like cellular launch pads that can promote concentrated viral assault. By eliminating these viral binding sites, Ellington says, “it should be possible to engineer the microbiome to prevent infections”—an approach he would like to pursue. “Had I not been exposed to her ideas in person, and been able to talk to her about her science, I would not have come up with the project.”

The scholars’ scientific diversity also makes it easier for them to open up about their work. “A lot of times you go to big meetings and people hold their cards pretty close to their chest,” says Mello. “But at Pew, you’re encouraged to brainstorm.” And given the scholars’ intellectual adventurousness, attending a meeting guarantees that “you’ll hear about amazing science from people who are at the cutting edge—a mix of ideas you would otherwise never encounter,” says Sandra Degen (class of 1987), who recently retired from her post at the Cincinnati Children’s Hospital Medical Center.

The meetings are held in quiet, remote settings that allow the scientists to escape their daily pressures and also foster casual conversations that can lead to what Rimel calls “an impromptu sharing of science.”

The resulting “five days of scientific fun is exactly what you thought a scientific life would be like back when you first decided you wanted to be a scientist,” says Ducy. Attending “really is a breath of oxygen.”

More than renewing enthusiasm and promoting intellectual exploration, the annual get-togethers have also spawned a number of close scientific collaborations. At the 2009 meeting in Puerto Rico, O’Toole struck up a conversation with Cornell University’s Holger Sondermann (class of 2008). “We were hanging out at the kiddie pool,” says O’Toole, who was spending time with his 18-month-old son while his wife, Deborah Hogan (class of 2005), also at Dartmouth, attended a session. “And we started talking about our common scientific interests.”

That poolside chat precipitated what has become a decadelong collaboration studying the mechanisms that allow microbes to come together in dense mats called biofilms, a strategy that can render them more tolerant of antibiotics. O’Toole’s team identifies the genes responsible, and Sondermann’s crew determines the structure of the relevant proteins, information that can point toward ways to interfere with biofilm formation. The collaboration has even helped them secure additional funding. “We’ve gotten great feedback from grant review panels for the fact that we’ve teamed up and can come at the problem from very different directions,” says O’Toole.

And theirs is not the only partnership to emerge from the scholars program. When Marnie Halpern (class of 1995) stumbled across a gene that was expressed exclusively on one side of the brain, she got in touch with fellow scholar Juan Carlos Izpisúa Belmonte of the Salk Institute for Biological Studies (class of 1996 and current member of the national advisory committee), who was working on the genes responsible for setting up left-right asymmetry in the rest of the body. That contact led to a publication and a collaboration “that might never have happened had I not met him at a Pew meeting,” says Halpern.

Some scholars maintain more than one Pew-based partnership, and some have also made connections with the program’s advisers. At dinner one evening, Ivo Ivanov of Columbia University (class of 2012) found himself seated next to Pamela Bjorkman of the California Institute of Technology, a 1989 scholar and current member of the national advisory committee. Talk quickly turned to their common interest in the molecular interactions that take place between host organisms and the bacteria that live within intestines, a conversation that has led to a grant and a manuscript in preparation. “It’s one thing if you write a letter to somebody to say you want to collaborate,” says Ivanov. “It’s another thing when you sit down and find common ground. That really makes things happen.” 

The Pew program also helps scholars find mentors. “When I received this award, I was an M.D. who had done six years of basic research, but I didn’t have the same sorts of contacts as other people who came from major programs or had powerful mentors who were invested in ensuring their success,” says Ian Lipkin of Columbia University (class of 1991). Through the Pew scholars program, Lipkin met Joshua Lederberg, who had been the first chair of the program’s national advisory committee. Lederberg shared the young scholar’s interest in emerging infectious diseases and offered Lipkin guidance as he worked to identify West Nile virus and SARS during those outbreaks. “In Josh, I found the mentor I never had—he completely transformed my career,” says Lipkin.

It does seem that Pew scholars turn to one another and to members of their community with great frequency, as evidenced by how often they end up citing their fellow scholars, says Jevin West of the University of Washington in Seattle, who maps the flow of information through scholarly communication networks to identify influential papers, journals, and individuals. Wading through the voluminous body of publications generated by the Pew scholars, West has confirmed that the impact of scholars’ collaboration is far-reaching. “Pew scholars, no surprise, are incredibly productive and incredibly influential in the biomedical field,” he says. And, he adds, “their most influential work is often done while they were funded by Pew.”

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Pew biomedical scholar Carol Greider won the Nobel Prize for physiology or medicine in 2009.

The success of the program has led Pew to create others as well. In 1990, under the guidance of Nobel laureate Torsten Wiesel, who served as chairman of the scholars’ national advisory committee for more than a decade, Pew launched a program for biomedical scientists from Latin America. Each year, 10 young researchers from Latin America receive support for postdoctoral studies in the United States, as well as additional funding to establish a laboratory when they return to their home countries. Wiesel remains chairman of the advisory board for the Latin American fellows, continuing a long tenure of leadership that Rimel says has been a hallmark of both programs.

The biomedical scholars program has also led to new collaborations for Pew. The late philanthropist Kathryn W. Davis believed in the promise of young scientists, and her legacy benefits the program today. And for the past three years, the Pew-Stewart Scholars Program for Cancer Research has funded early-career scientists whose research is leading toward a cure for cancer. Pew administers the program funded by the Alexander and Margaret Stewart Trust, which has long been committed to cancer research and prevention.

The biomedical scholars program’s 30 years of success has not only led to these new opportunities but also led the scholars themselves to enlarge their roles beyond their laboratories. During their scholarship years, they are actively encouraged to reach out and extend their influence to the betterment of society. “Scientists can go their whole career only talking to other scientists,” says Mello. “But communicating with the broader community is so fundamentally important. Without it, the scientific enterprise is going to break down. For me, that really resonates, and it has really helped me, in the years since the Nobel, be more engaged with society at large. I felt better prepared for that because of my training as a Pew scholar.”

Scholars have been inspired to write letters to the editor or explain issues to members of Congress or meet with governmental health agencies like the National Institutes of Health. “There was just this different kind of attitude toward being a scientist and putting your work in the context of humans, rather than just going to the lab and doing your experiments,” says Bjorkman, who used her experience as a Pew scholar to inspire the lectures she gave in the California Institute of Technology’s undergraduate biology course for nonmajors.

“We really do encourage the scholars to get involved in science policy, get involved in issues in their community, and speak out on issues relating to science in the public policy arena,” says Rimel. “So we are pleased to see that they have taken this to heart and that they are exercising their leadership in a broader civic way.”

The Pew scholars “instill a sense that you have to go beyond the research to advocate, educate, or in some way give back,” says Phil Hieter of the University of British Columbia (class of 1986). And over time, he says, “that’s going to have an effect” on the world.