High risk projects yield big rewards at NIH

Elizabeth Wilder, Director, Office of Strategic Coordination at NIH

When the National Institutes of Health comes across an idea that seems too big, or too risky, for traditional modes of scientific investigation, the agency turns to its Common Fund program. This is where high risk, high reward programs that no organization would ordinarily take a chance on can find funding. And it’s paying off.

The Common Fund began in 2004, when NIH’s then-Director Elias Zerhouni called on the directors of various institutes and centers within NIH to create a corporate strategy for scientific planning. These directors all brought programs designated as high risk, high reward to the table, and together they decided to devote one percent of NIH funding to them.

“It’s not a small amount of money, but it’s a small percentage,” said Elizabeth Wilder, director of the Office of Strategic Coordination at NIH said on week one of the Themed Month, featuring Advances in Health Care for the month of September.

Nevertheless, that small percentage is paying big dividends in the world of health care research. Dividing into four separate initiatives in the dozen years since its inception, the Common Fund has been responsible for research that has changed — or promises to in the near future — how healthcare professionals and citizens alike think about health care.


“One of my favorite programs has been the human microbiome project,” Wilder told Federal News Radio’s Tom Temin. “The human microbiome project sought to understand all of the microbes that live in and on human beings, and to establish how diverse that ecosystem of microbes are and what they do for human biology.”

This project is where all the recent emphasis on “good” versus “bad” bacteria has come from, not to mention the proliferation of such products as probiotics.

Wilder said that the program still is ongoing, and there’s a good deal more research to be done before scientists understand all the implications of the project. For example, she said, researchers are just beginning to understand the connections between the bacteria in the stomach and the functioning of the brain.

Personally, she said the research has made her much more accepting of the microbes in and on her body.

She said it’s programs like these which can’t stand up to the peer review process, but have the potential for huge payoff.

“One of the hallmarks of the programs we support is risk,” she said. “It is a fine line. We want them to be feasible.”

But peer reviewers, she said, like having the freedom to embrace these big ideas.

Another such big idea is research into floating RNA (ribonucleic acid), a strand of amino acids that is used to copy DNA (deoxyribonucleic acid).

“One example is we are supporting a program now to try to understand the function of molecules that circulate in our bloodstream and cerebrospinal fluid that are RNA molecules that for decades scientists really thought only lived inside a cell,” Wilder said. “But we now know they float around, and we know they can be taken up by other cells, and they have a function. But we don’t really understand what those functions are.”

Wilder said that the idea of free-floating RNA, which circulate and provide functions remotely, is a new concept that includes a level of risk most peer review groups aren’t willing to take. So it falls to the NIH Common Fund instead.

Another example of such a program is the genotype tissue expression research, or GTEx project.

In this case, Wilder said, a number of studies across NIH correlated changes in DNA sequence with susceptibility to many diseases. But the changes didn’t lie within the genes themselves, but in “mystery DNA” that exists outside, much like the aforementioned free-floating RNA.

But because the research required tissue from organs like the heart and liver, locating living donors was problematic. So, through the Common Fund, NIH coordinated a program to collect cadaveric tissue samples and perform strict quality control measures. Now the research is starting to produce correlations.

The most basic requirement of programs like these, besides the high level of risk, is that they must support science that is relevant to many or all institutes across NIH. Similarly, the research may be conducted by many different institutes, or even outside research organizations. In fact, Wilder said, much of the funding for these programs goes outside the NIH.

It falls to the Office of Strategic coordination to bring all these disparate parts together, organizing these collaborative efforts into a holistic picture that can change the landscape of health care. It’s a particularly exciting division of what many already consider to be an exciting agency, Wilder said.

“I think probably the best job with NIH is probably the NIH director’s job,” Wilder said. “But I like my job a lot.”