Once and Future Funding

Last year, Junying Yuan, HMS professor of cell biology, was facing a common impasse in highlevel science. Her highly rated grant application had narrowly missed the low pay-line cutoff imposed by years of virtually flat federal science budgets and inflationary erosion of research support.

Within months, a surge of federal stimulus money helped rescue part of Yuan’s proposal and saved two research jobs in her lab. The extra support has allowed Yuan’s expert team to nudge a fundamental discovery about cell death one step closer to clinical testing for potential treatment of neurodegeneration and infection.

Many of Yuan’s colleagues have similar stories, thanks to the American Recovery and Reinvestment Act (ARRA) of 2009, which committed an extra $21.5 billion to support science funded by federal agencies. Researchers in the Harvard medical community can measure the substantial impact, even as they hear the clock ticking down on the critical two-year infusion of funding.

By the most recent count, $82 million in stimulus funding supported 113 projects and created or retained the full-time equivalent (FTE) of 111 jobs at HMS alone, which accounts for just over half of Harvard’s Recovery Act funding. HSPH received $30 million for 41 projects, supporting 25 additional FTEs. The University totals are generally matched at comparable biomedical research institutions in Boston and elsewhere, including some HMS affiliates.

“This investment in science is not only creating jobs, it is unclogging the arteries of innovation,” said Kevin Casey, associate vice president for government, community and public affairs at Harvard. “The quality of the research funded by the grants demonstrates the incredible pent-up scientific demand that has accumulated in the last five years of stagnant federal funding. It speaks loudly for the need to raise the bottom line on National Institutes of Health (NIH) funding consistently in the post-ARRA era if we are to take full advantage of this important one-time investment.”

The Recovery Act funding came embedded with a financial cliffhanger. “Everyone is concerned about what happens in two years when the bolus of funding from the stimulus runs out,” said Joan Brugge, chair of Cell Biology at HMS. “A lot of scientists are going to be seeking additional funding all at the same time. It’s not clear what is going to happen to keep those people employed and those projects going.”

In the short term, the breaks in funding can derail projects and careers, especially affecting young scientists, Brugge said. Over the long term, the uncertain funding can discourage smart people from going into science, destabilize the biomedical infrastructure, challenge U.S. leadership in science and threaten the associated innovationdriven economic growth, Brugge and others say.

Over a recent decade, for example, China posted an average annual 20 percent growth rate in federal research and development, compared to the U.S. average growth rate of 5 to 6 percent, according to the 2010 Science and Engineering Indicators digest from the National Science Foundation (NSF).

The nation’s medical enterprise needs sustained, predictable growth to find new cures and treatments, to strengthen the U.S. economy by creating skilled and high-paying jobs, and to produce new products, industries and technologies, urges the Association of American Medical Colleges

The funding necessities reflect the time and consistent effort it takes to crack complex scientific problems. Ten years ago, for example, Yuan’s team began the work that eventually revealed a third major way that cells die in diseases and chronic conditions, called necroptosis or programmed necrosis. The Yuan lab identified the only known family of small molecules, called necrostatins, that can completely block this cell death pathway and allow the cell to survive. In the next stimulusfunded step, Yuan’s team will be looking for biochemical markers of necrostatin activity to more easily monitor the drug action during testing in people. The studies may also reveal the soughtafter downstream executioner proteins for greater understanding of the cellular death process.

The U.S. President’s budget request for FY 2011 does not answer all the funding questions, but it “has to be seen as good news” in a budget that froze spending on most federal programs, according to an analysis from Casey’s office. Released in February, the request seeks a 3.2 percent increase for the NIH and an 8.2 percent increase for NSF research and related activities. The amounts represent a continued commitment to science and innovation in a budget that otherwise responds to record-high federal deficits by instituting a freeze in the domestic discretionary budget that, among other things, funds most university education and research programs, the analysis concluded.

The proposed increases start from the 2010 appropriations and do not include the one-time Recovery Act funding (which would translate to a 30 percent increase in the NIH’s $30 billion budget). “Next fiscal year will therefore be the first year where we begin to grapple with a ‘hangover’ effect from the stimulus infusion,” the analysis said.

In the meantime, for Yuan, the stimulus funding gives the most exciting and interesting experiments a fighting chance to accomplish important goals, said Konstantin Salnikow, Yuan’s program director at the National Cancer Institute. Yuan’s original five-year proposal has been scaled back to accommodate a two-year funding plan.

Her immediate task is almost allegorical. Temporarily saved by the stimulus funding, Yuan’s expert team is seeking to block the death-defining enzyme known as RIP1 kinase. “The question is,” said Yuan, “what happens after two years?”

For more information, students may contact Junying Yuan at junying_yuan@hms.harvard.edu.

Conflict disclosure: The necrostatins have been licensed by TetraLogic Pharmaceuticals, for which Junying Yuan is a consultant.

Note: Harvard University’s Government, Community and Public Affairs Office is encouraging all ARRA funding recipients to contribute examples of individual and collective contributions from ARRAfunded projects for its Spotlight on Science Initiative. For more information, contact Kelly Ciccolo, HSPH stimulus specialist, at kciccolo@hsph.harvard.edu.