Rewards of Risk

The award marked a shift in Lieber’s research career, he says. Two years later his team published a breakthrough invention—a virus-size probe that can enter a cell and monitor action potentials without affecting the cell’s structure (Science, 329:830-34, 2010). “I had a lot of these ideas for years,” says Lieber, “but this would have been really, really difficult without the Pioneer.” Today, more than half his team works on cell-nanoelectric interfaces.

NIH will invest at least $108 million in visionary research this year through its four high-risk grant programs: the Pioneer Award, the New Innovator Award, the Transformative R01 Program, and the EUREKA Awards. Numerous other organizations also offer awards for innovative projects (See sidebar on opposite page: “Beyond Federal Funding”). Such awards “try to allow people the opportunity to pursue an out-of-the box idea,” says Ravi Basavappa, manager of the Transformative R01 program in the Office of the Director at NIH. But because of their popularity, “the competition is quite keen,” he adds.

To give you a leg up on the competition, here are some tips for securing your own high-risk grant, including advice from researchers who took one home, and the inside scoop from NIH itself.

Straight from NIH: Tips from the top

Make them call you crazy

At a 2008 retreat, engineer Andrea Armani of the University of Southern California (USC) overheard researchers complain about the difficulty of trying to measure DNA methylation using PCR. “I should come up with a better way of detecting [DNA methylation] so you don’t need PCR,” Armani told them. “That’s impossible,” they replied, staring at her as if she were crazy. But NIH didn’t think so: last fall, Armani was awarded a New Innovator Award—$1.5 million over five years to develop a nanolaser capable of detecting methylation of a single strand of DNA.

Nothing in your application is more important than the big idea, says Judith Greenberg, principal leader of NIH Director’s Pioneer and New Innovator Awards. “There’s no substitute for presenting a truly, highly innovative idea,” she says. Without that, “nothing else that you do is going to matter.”

Dig up your best science-fair projects

A great idea is the first step, but the second is to convince a reviewer that you’ll be able to deliver. Reviewers for the Pioneer and New Innovator Awards want applicants to demonstrate evidence of past innovativeness. Since preliminary data is not required, the reviewers will want examples of your past creative, groundbreaking research to vouch for you. The NIH recognizes that many applicants, especially for the New Innovator Award, are young investigators without long track records, so don’t be afraid to strut your stuff from postdoc or even graduate school days, says Greenberg. “We just want some indication of how they think and whether they are really creative, innovative people,” she says.

Get a hotel room

“It’s tricky,” says Valentin Dragoi, a neurobiologist at the University of Texas Medical School at Houston and winner of a 2010 Pioneer Award. “Sometimes with complexity, we hide how cool an idea is.” To keep himself on task while at a conference, Dragoi closeted himself in a hotel room for three days to write his grant application. “It was miserable but it paid off in the end,” he said—the isolation worked well for writing. In particular, Dragoi tried to constantly remind himself to think about the big picture.

Skip the all-star recommendation

Applicants sometimes submit letters of recommendation from big names in their field, yet these letters are often the weakest because the authors don’t always have a close relationship with and detailed knowledge about the applicant. “It’s generally better to have someone who knows you well [write the letter], even if it’s not somebody who is a household name,” says Greenberg. Details are valuable, agrees Dragoi: “the letters of reference should attest to your ability to solve problems, and point out when you’ve been successful.”

How they did it: five grant writing tips

1. Keep it simple

Explaining the physics of a nanolaser capable of detecting DNA methylation is not necessarily a simple task, but USC’s Armani made it her mission to write the five-page essay required for a New Innovator Award using language that was as jargon-free as possible.

“Make it easy on the reviewers,” says Armani. “Literally make a heading in the proposal that says, ‘This proposal is innovative because it ____,’ and fill in the blank.” After completing her essay, Armani asked friends to read it to assure that it was simple and convincing before she submitted the grant.

2. Document…with pizza

To prove an idea is truly innovative, it’s important to thoroughly document research in the area, emphasizes Dragoi. But reading your weight in papers isn’t something you have to do alone. For his Pioneer Award grant application Dragoi reached out to students and postdocs in his lab to help find and document all the papers he would need to demonstrate that the project proposal was novel (and grad students often work better when plied with pizza). “People shouldn’t be afraid to ask their postdocs and students, who understand the game, to help with good documentation,” he says. Although many grant applications restrict the length of citations, it’s important to know what’s out there, adds Dragoi, so you can confidently assert that your research will be novel.

3. Reduce the risk

At Brigham and Women’s Hospital, Nathalie Agar wanted to develop a mass spec that could be fitted into a surgical probe to collect cellular data in real time. The information would help identify the margins of a brain tumor, allowing neurosurgeons to make more accurate cuts. In her application Agar acknowledged these risks, but then emphasized her training with a neurosurgeon who helped pioneer an MRI used during surgery, and cited Brigham and Women’s track record for creating innovative neuroimaging tools. She made it clear in her application that the risks were “well-calculated and buffered by all these different components.”

4. Show your planning

A Bill & Melinda Gates Foundation Grand Challenges Explorations winner, Transderm Inc., is developing a painless, low-cost, no-refrigeration vaccine delivery system that could increase vaccine access to at-risk populations, and potentially improve vaccine efficacy. COURTESY OF THE BILL & MELINDA GATES FOUNDATION

Any project, even one labeled “high risk,” has to be realistic, so make an effort to show the details of how it can be done, says Agar. “Writing the essay, I was almost putting together a business plan,” she notes, setting forth a concept and then profiling how she intended to fulfill it, including a feasibility assessment, and describing the potential market for the surgical probe. In addition to her training and collaborators, Agar described who would manufacture the parts of the probe, where in a hospital it could be used, and why it would be attractive to doctors. “You have to be very strategic about why you are in a position to make this work,” says Agar.

5. Never, never, never give up

“Keep plugging away,” says Martin Blaser, a microbiologist at New York University School of Medicine. He wanted to design a vaccine against cholera and Campylobacter bacteria, both of which cause serious diarrheal diseases. His plan was to engineer a harmless version of the gut bacterium H. pylori to deliver the protective antigens, but the Gates Foundation wouldn’t bite. After being rejected twice for a Grand Challenge grant, Blaser resubmitted his application a third time without even revising the proposal and it was funded.

But be warned, NIH has a policy of not accepting applications that have not been specifically changed, says Greenberg. So if you’re submitting to NIH, revise at length ahead of time.