Eun Ji Chung, PhD, had a vision—a nanoparticle delivered intravenously that would detect atherosclerosis, the potentially deadly build-up of plaque in arteries, administer therapy and signal whether the treatment has succeeded.
The young biomedical engineer is a postdoctoral fellow in the lab of Matthew Tirrell, PhD, dean and founding Pritzker Director of the Institute for Molecular Engineering at the University of Chicago. In 2013, she applied for a K99/R00 Pathway to Independence Award from the National Heart, Lung and Blood Institute (NHLBI) to develop the so-called “theranostic” nanodevice. The five-year, $900,000 grant provides for two years of mentored research followed by three years of self-directed work. Chung’s project to open a new front in preventing and treating heart disease would launch her career as an independent investigator.
But, like roughly 78 percent of applicants for these awards across NIH agencies that year, Chung missed the cut. Undeterred, she enrolled in the new Career (K) Award Writing Workshop offered by UChicago’s Institute for Translational Medicine. For three months, Chung and three other postdoctoral researchers turned down for funding were put through their paces for 90 minutes a week by neuroscientist Harriet de Wit, PhD, and physician-scientist Steven White, MD. Between them, the faculty members count decades of experience winning federal awards. White had also just completed a stint chairing the NHLBI study section overseeing the grant Chung sought.
“Eun Ji is a superb young scientist,” he said. “There’s little I can tell her about her area of science she doesn’t know.”
What the faculty members could offer were insights into how to craft a compelling proposal: cueing the postdocs to what study sections look for, advising them on fixes to parts of their applications dinged first time round and generally serving as proxies for real-life agency reviewers.
“The grasp the class gave me of the intricacies and nuances of grant writing was invaluable,” Chung said. Last November, Chung’s re-tooled proposal was approved. Development of the nanodevice is underway.
And the Pathway to Independence Award lived up to its title. Chung fielded offers from multiple institutions before accepting an assistant professorship in biomedical engineering at the University of Southern California, starting next September.
Moment of opportunity
Chung’s work exemplifies the emerging possibilities in biomedical research. Employing principles from physics and engineering to harness the remarkable properties of matter at the molecular scale, nanomedicine scarcely existed 15 years ago. It’s not an outlier; new technologies and approaches abound. For example, the CRISPR-Cas9 gene editing system confers exquisite control in manipulating basic biology to pinpoint the function of genes and proteins, as well as to potentially devise new therapies. Meanwhile, high-throughput sequencing, digital imaging and cloud computation herald a massive quickening in our ability to acquire and analyze biological data.
To prepare for biology in the age of big data, members of the incoming Biological Sciences Division graduate class convened at the University-affiliated Marine Biological Laboratory in Woods Hole, Mass., in September for an inaugural pre-term boot camp on computation and statistics. Attendance at the weeklong intensive was mandatory for most students. “The University is making a big investment,” said Victoria Prince, PhD, dean for graduate education and professor of organismal biology and anatomy. “We’re building on this by developing new courses on campus. Quantitative methods are integral to modern biology; students need to be ready for the exciting times ahead.”
But Chung’s story also demonstrates the financial backdrop to these unfolding opportunities.
In 2013, she found herself among more than 2,000 applicants turned down for career development funding from the National Institutes of Health (NIH), which doled out almost $33 million less for these awards that year compared to 2005.
NIH funding for biological and medical research is the fiscal backbone of the basic, translational and clinical biomedical research performed by the nation’s universities. Accounting for inflation, it has declined in spending value by 22 percent since 2003, according to the Federation of American Societies for Experimental Biology. At the same time, more investigators than ever are chasing fewer dollars. From 1998 through last year, the number of grant applications more than doubled.
Competition for awards is correspondingly stiff. In 2001, almost one in three applications won NIH funding. Last year, slightly more than one in six proposals were approved. The situation is especially bleak for first-time applicants competing against senior colleagues for scarce funds. Despite dispensations intended to level the playing field, their rate of success in securing RO1 grants in 2014 was approximately one in seven.
Also hard hit is basic science. In 1990, basic science accounted for almost three-quarters of NIH research spending; this year it is projected to make up a little over half. Amid an emphasis on translational research offering the prospect of more immediate returns, funding for fundamental research has fallen more than 13 percent since 2006, after inflation is factored in.
The fallout is being felt at UChicago as it is on every other research campus. Although it rebounded slightly in fiscal 2015, NIH funding for University research declined by 14 percent from fiscal 2009 to fiscal 2014, before inflation is taken into account.
“The potential through sequencing, computation, imaging and other technologies for breakthroughs that improve health, prolong life and reduce suffering has never been greater,” said Kenneth S. Polonsky, MD, the Richard T. Crane Distinguished Service Professor of Medicine and Dean of the Biological Sciences Division and the Pritzker School of Medicine. “Yet the government’s commitment to funding the work needed to produce these breakthroughs has never been weaker.”
As a result, the University is not only helping researchers master the skills they need to flourish in a new scientific landscape but also those necessary to navigate a new financial one. Along the way, it is extending a hand to strapped investigators, tapping new sources of funding and taking its message about the importance of robust government support for research to lawmakers.
Smarter proposals sooner
The writing workshop that helped Chung beat the odds forms part of a phalanx of institutional initiatives to help faculty build the strongest case for federal support in an environment where little can be left to chance.
This requires turning what has long been something of an art into a science, moving beyond an impressionistic grasp of what makes a winning proposal toward a more data-driven understanding.
A key tool in this endeavor is the 11-person Federal Funding Working Group convened in July by the Office of the Provost and slated to report to senior institutional leaders this fall. Comprising administrators and academic leaders from multiple divisions, the panel is tasked with identifying ways to boost faculty competitiveness for federal awards, with a particular eye toward improving the University’s standing relative to peer institutions.
“We’re analyzing data on proposal submissions and awards over years to identify trends and drivers, and categorize the reasons behind unsuccessful submissions,” said Jessica Lawrence, director of pre-award services and co-chair of the group. “We want to identify where we’ve been successful, where we haven’t and the reasons behind both.”
Complementing this exercise is an expanded role in proposal preparation for University Research Administration (URA), the University’s grant management unit. This will allow faculty to farm out the administrative components of applications — project budgeting, logistics and regulatory compliance — to concentrate on the scientific content, said Michael R. Ludwig, associate vice president for research administration and URA director. “The traditional role of our office is to vet proposals for compliance. We’re trying to provide more centralized support from the start of an application. We want to handle the administrative parts of proposals, so faculty can focus on technical writing about their projects.”
Matchmaking in D.C.
Another prong in the effort to enhance faculty members’ competitiveness for awards involves helping them “get to know their customer — the agency from which they’re seeking funding,” said Eric D. Isaacs, provost of the University of Chicago.
Based in Washington, D.C., Kate Von Holle serves as director of federal research development — the University’s dedicated liaison to the NIH and other funding agencies.Th e role, created in 2013, places UChicago among a select but growing cadre of campuses retaining such representatives.
Von Holle funnels news of funding opportunities back to campus and relays updates on new directives that might affect grant eligibility. She also helps faculty navigate agencies’ idiosyncrasies — brokering meetings for them with key personnel — and generally serves as matchmaker between agencies and researchers seeking funding.
“I try to meet as many faculty as possible to get a sense of what people are doing and how I can help,” said Von Holle, who has already had discussions with more than 100 faculty members. “I also have meetings on the agency side to understand their priorities and how they might manifest in funding opportunities.”
One beneficiary of this networking is Andrey Rzhetsky, PhD, professor of medicine and human genetics.
Rzhetsky employs artificial intelligence tools to parse research papers, electronic medical records and other datasets for fresh insights into disease. In February 2014, he learned of a prime funding opportunity with the Defense Advanced Research Projects Agency (DARPA) to apply the technique to cancer data. Together with Von Holle, Rzhetsky met with DARPA officials to get a tighter fix on what the agency was looking for.
“Kate organized meetings in which we collected information about how these proposals are written,” he said. “It wasn’t about the science; it was about how to frame the science and what to put in the proposal.” Rzhetsky also drew on expertise from Arete, the University’s research accelerator, with which Von Holle is affiliated, for his submission. “They helped me with the non-scientific components of the proposal, such as the management plan — how the project would be structured and who would do what,” he said.
Last summer, Rzhetsky and his team got the nod — $4.5 million to develop computational algorithms that can mine research literature for testable models of the protein interactions behind cancer toward identifying prospective new therapies.
“Better still,” Von Holle added, “through the meeting process, Andrey met a bunch of new people, some of whom he’s stayed in touch with.”
Such activity forms part of a longer game. Beyond immediate funding opportunities, Von Holle is working to put UChicago investigators on the radar of grant-issuing officials, positioning them as thought leaders and generally raising the University’s profile with those holding the research purse strings.
“I call it ‘socializing’ agencies to the work of the University,” she explained. “The ultimate goal is to get more people interested in and aware of the work happening at UChicago. This kind of influence is a long-term play, but it’s important for the University because there are a lot of other universities active and engaged in D.C., promoting their faculty work.”
Bridge to impact
Here on campus, the University is nurturing research that might otherwise fall through the cracks.
One practical effect of the funding downturn, investigators say, is reticence on the NIH’s part to commit tight funds to research not already substantially advanced toward its goal.
Researchers can find themselves in a chicken-and-egg situation: needing funds to prove the viability of a hypothesis, but unable to secure them for lack of proof. Among the casualties can be potentially transformative work. “Study sections are looking for researchers to confirm the feasibility of their approach,” said Prince. “It rules out a lot of cutting-edge stuff.”
T. Conrad Gilliam, PhD, the Marjorie I. and Bernard A. Mitchell Professor and dean for basic science, estimates that up to one in 10 BSD faculty have received “bridge” funds to ease this quandary and, more generally, sustain them between federal grants. The principle behind the awards is simple: impetus to acquire more data and prove a concept toward securing federal funding. In this way, relatively modest infusions can yield outsize returns.
In 2011, Richard P. Kraig, MD, PhD, the William D. Mabie Professor in the Neurosciences, had a provocative proposal for a new way to treat migraines and multiple sclerosis based on a naturally occurring substance within cells that repairs neural damage. But the NIH deemed it “too far out on the edge,” he recalled.
Putting $150,000 from the BSD to work, Kraig built out his dataset and substantiated the hypothesis, parlaying it into $4.1 million in grants from the NIH plus $100,000 from the National Multiple Sclerosis Society and $300,000 from UChicagoTech, the University’s center for technology development and ventures.
“We got the data we needed to establish proof of principle and secure the federal funds,” Kraig said.
Thanks to $3.5 million from the John Templeton Foundation, another mechanism for incubating early-stage research has been Arete’s Big Ideas Generator (BIG) program. Over the past year, this has disbursed small grants for pilot or proof-of-concept studies and $100,000 awards for projects that are further along but need more data.
“We’ve tried to make risky ideas less risky by helping researchers get preliminary data to bring to the NIH,” said Jasmin Patel, MBA’12, Arete’s executive director. Borrowing from Silicon Valley, where venture investors bootstrapping tech startups also provide them with business guidance, Arete has taken a hands-on approach to funding. “It’s about more than giving investigators money,” said assistant director of research innovation Meera Raja, PhD. “We sit down with them to discuss what the project will look like down the road and the opportunities for future funding.”
Now, Arete is adapting the online application system developed for the Templeton-funded awards into a portal for seed funding opportunities University-wide. Awards will remain at the discretion of divisions and departments, but the new web offering will provide a one-stop shop through which faculty can apply for them. “This is about streamlining the application process and making seed awards more easily discoverable for faculty,” Patel said. The service, slated to be operational as early as fall 2016, will also allow officials to better coordinate seed funding across campus and track demand for it more precisely.
Arete also offers a lever for generating bold, often cross-disciplinary projects that can contend for substantial federal funding opportunities through quarterly brainstorming sessions it convenes to spur faculty to come up with creative solutions to tough problems. “The premise is to have a bunch of people propose and debate ideas for big things, then figure out the teams we can pull together to make them happen,” Isaacs said.
At the same time, the University is cultivating funding sources beyond the federal government.
One such income stream comes from research-driven inventions that may either be licensed to corporations or spun out into start-ups, in many cases involving the faculty investigators themselves.
UChicagoTech brought in $5.8 million from commercializing intellectual property in fiscal 2015 — a significant portion of which was plowed back into the research enterprise.
The University also pursues industry-sponsored research. Over the past 11 years, corporate backing of BSD research tripled to more than $55 million. Funding for clinical trials accounted for 83 percent of industry research support in the BSD in fiscal 2015 and the University is proceeding cautiously beyond trials, emphasized URA’s Ludwig. “Like our peer institutions, we’ve chosen not to accept funding that restricts our ability to publish research findings.”
Still, industry-sponsored clinical and translational research represents an important and growing part of BSD’s research portfolio.
Again, UChicagoTech is helping drive this activity. “We’re the interface between what’s happening in University labs and the business world,” said deputy director Steven Kuemmerle, PhD. At this year’s BIO International Convention in Philadelphia, UChicagoTech delegates met representatives from more than 80 companies, he said. “While we’re out there shopping the University‘s technology, we’re spotlighting UChicago investigators and their capabilities.”
A so-called “master sponsored research agreement” negotiated by UChicagoTech and URA with Bristol-Myers Squibb (BMS) in 2012 provides several million dollars for University research in cancer immunology, a promising new paradigm for cancer care that enlists the immune system to fight tumors as it would a virus. The pact grants BMS certain preferred rights to develop any discoveries arising from the funded research.
The gift of philanthropy
Another lifeline for research is philanthropy. Last year, the University publicly launched its biggest capital campaign yet, targeting $4.5 billion in charitable gifts, including a goal of $1.2 billion for medicine and the biological sciences.
“We’re seeing a boom in foundation support,” said Peter H. O’Donnell, MD’03, assistant professor of medicine, who uses philanthropic awards to advance his research into how genes affect patient response to chemotherapy. “They’re real grants, offering hundreds of thousands of dollars. I see them as equivalent to federal grants; they allow you to do your research. They’re a great way to grow your career.”
As a corollary, such funds improve investigators’ prospects for securing federal awards. Agencies look favorably upon philanthropy because of the momentum it builds behind work, Isaacs said. “Philanthropy is important for federal awards because agencies like to see leverage on their dollar.”
Philanthropy is also a potent source of innovation in funding models. Many philanthropic gifts target pain points, neglected niches and areas of acute need in the current funding climate.
For example, the W. M. Keck Foundation, which has previously supported work in molecular biology among other research at the University, expressly solicits novel ideas that would be a hard sell to risk-averse agencies. Among other criteria, the projects they fund must “demonstrate a high level of risk due to unconventional approaches, or by challenging the prevailing paradigm . . . have the potential for transformative impact [and] fall outside the mission of public funding agencies.”
Meanwhile, the $150 million Faculty Scholars program, announced earlier this year by the Bill & Melinda Gates Foundation, Howard Hughes Medical Institute and Simons Foundation, extends support (up to $2 million over five years) to young tenure-track scientists, buying them time away from the grant-writing treadmill to double down on their research during a formative stage in their careers.
“You have to be creative and look at different sources of support in this funding environment,” said O’Donnell, himself a 2010 recipient of the Cancer Research Foundation’s Young Investigator Award, intended “to enable promising young investigators to initiate successful scientific careers.”
The imperative of NIH support
But the University is not taking its eyes off the ultimate prize: restoration of NIH research funding to historic levels.
At over $218 million, funding from the NIH represented more than 45 percent of the $468.7 million the University was awarded for research in fiscal 2015.
The importance of NIH funding extends beyond its sheer magnitude. Faculty affirm the primacy of the federal government as a source of disinterested support for research, particularly basic science —the benefits from which may not be felt for decades — for which there can be scant other funding options.
“Government funding is critical because it serves the entire population,” said Julian Solway, MD, the Walter L. Palmer Distinguished Service Professor in the Departments of Medicine and Pediatrics and director of the Institute for Translational Medicine. “The government alone can allocate funding broadly enough to create the portfolio of research we need. The incentives for industry are inadequate, and philanthropy, while tremendously important, tends to be focused on specific areas.”
Polonsky recasts NIH’s budget, almost $30.1 billion in 2014, as a percentage of total U.S. health care expenditures — projected to reach $3.1 trillion for 2014. “We’re talking about increasing the amount we spend on research, now around one percent of our total health care investment, and the impact would be profound.”
“We need a robust pipeline of NIH-funded basic discoveries that industry can apply to make medical advances,” he added. “Without basic science discoveries, you choke off the entire ecosystem.”
Spurred by such considerations, the University is flexing its advocacy muscles.
In Washington, Von Holle forms part of a five-person Office of Federal Relations, established in 2008. “We are very engaged in educating a wide variety of groups on the impact of scientific research on human health and the importance of federal funding in supporting the national research efforts,” Polonsky said. “This includes meeting with members of Congress.”
In spring 2014, the University threw its weight behind legislation proposed by Richard Durbin (D-Ill.)to ease the funding crunch. The American Cures Act would peg increases in the budget of the NIH and other federal granting agencies for biomedical research to inflation plus a premium of 5 percent, injecting approximately $150 billion over a decade. To herald its endorsement of his bill, the University hosted Durbin on campus for a roundtable discussion with faculty and students.
In May, Polonsky joined 18 other deans of leading academic medical centers as a signatory to an op-ed in Science Translational Medicine protesting the decline in federal support and calling for a “stable economic platform” for biomedical research.
Grounds for cautious optimism
In the meantime, the prospects for such support are finally looking up.
Following years of gridlock, political will is building behind increased research spending amid a convergence of factors, said Mary Woolley, president of advocacy group Research!America, a member of the Visiting Committee to the BSD and the Pritzker School of Medicine, and a longtime observer of the Washington scene.
In June, the House of Representatives approved the 21st Century Cures Act, which like Durbin’s bill before the Senate would boost NIH’s budget. At the same time, the broad coalition of support coalescing around hiking funding for NIH spans liberal Democrats as well as conservative Republicans who have embraced a well-funded NIH as a tenet of fiscal conservatism — a hedge against incurring greater expense from health care costs down the road.
Woolley also notes an increased sense of urgency around research amid mounting anxiety over Alzheimer’s. “Existential threats are an important driver of NIH funding,” she said. “Concern over HIV/ AIDS was one, the War on Cancer another and, before that, polio.”
Finally, she sees in CRISPR-Cas9 a breakthrough technology with the potential to grip the imagination and energize lawmakers as the Human Genome Project did in the 1990s.
“There remains a lot of work to do on many people’s parts,” Polonsky said. “But sooner or later people will realize we’re doing more harm than good by focusing exclusively on the cost of research.”
“This is not a political philosophy,” he added. “It’s about a belief in science and medicine — the power of scientific discoveries to advance medicine.”
This story was originally published in the Fall 2015 issue of Medicine on the Midway.