When she arrived at Yale after a successful postdoctoral fellowship, Megan C. King, Ph.D., assistant professor of cell biology, was ready to hit the ground running. But she soon found that setting up a brand-new lab isn’t easy, and has a lot in common with starting a small business from scratch. “You have to find the people, you have to find the ‘investment’ money, you have to decide what your ‘products’ are going to be, and then you have to get something done so you can return something to those investors,” King says. “And that is not at all what being a postdoc is about.”

For new investigators it’s always been a challenge to win grants. But today even experienced researchers are facing funding cutoffs, making it all the more difficult for those just starting out. Fortunately, corporations, foundations, and private individuals are stepping into the breach, offering young investigators welcome supplements and even alternatives to federal funds. And the federal government itself is following suit, establishing funding streams specifically tailored for gifted scientists in the first stages of their careers. While these funding avenues are no substitute for bread-and-butter federal research grants, they provide a measure of relief to a select group of investigators.

For example, in 2011 King was named a Searle Scholar, an honor awarded to 15 new tenure-track scientists annually that supports their work with a gift of $300,000 over three years. Funded by the estates of Mr. and Mrs. John G. Searle, the Searle Scholars Program supports exceptional young faculty in the biomedical sciences and chemistry. King’s recruitment to Yale in 2009 was also supported in part by the G. Harold and Leila Y. Mathers Charitable Foundation, which awarded her $1.1 million over three years for her work using fission yeast to study the DNA repair functions within cells.

This spring, Andrew Goodman, Ph.D., assistant professor of microbial pathogenesis, and Bo Chen, Pharm.D., Ph.D., assistant professor of ophthalmology and visual science and of neurobiology, were named 2013 Pew Scholars in the Biomedical Sciences. Offered to just 22 scholars nationwide, the prestigious prize from the Pew Charitable Trusts offers $240,000 over four years, and is awarded only to early-career scholars. Elena Gracheva, Ph.D., a new assistant professor of cellular and molecular physiology, runs her lab with the help of grants from the Alfred P. Sloan Foundation, the Arnold and Mabel Beckman Foundation, and the Rita Allen Foundation.

Through the Yale Scholars program, founded in 2006 by Dean and Ensign Professor of Medicine Robert J. Alpern, M.D., donors contribute $2.5 million, which is matched by Yale to establish a named $5 million fund that provides $1 million in startup funds over four years to a promising new tenure-track investigator. Donald S. McCluskey, M.Eng., an alumnus of Yale College and Yale’s Faculty of Engineering, endowed the first Yale Scholarship in the name of his brother (now deceased), Robert T. McCluskey, M.D., also a Yale College alum. Goodman was named the McCluskey Yale Scholar in 2011, an honor that helped him get his lab off the ground in its earliest days.

These initiatives are more important than ever because federal grants—traditionally the largest source of funding for the biomedical sciences—are extremely difficult to land now for all researchers, but especially for junior scientists. “It used to be easy: Do decent work, put in a reasonable grant, listen to the comments, resubmit it maybe once, and you’ll get an R01—and the expectation was that within five years you’d get a second R01,” King says, referring to the National Institutes of Health’s (NIH) sought-after renewable grants. “That’s no longer really feasible.” The statistics bear her out: in 2001, the renewal rate for R01s was 51 percent, but in 2012, it was 33 percent.

For scientists of all ages submitting proposals for new R01s, prospects are even grimmer. In 2001, the NIH funded 25 percent of new R01 grant applications; in 2012 funding had declined to 15 percent, and within some individual NIH institutes, the success rate has dipped into the single digits. Yet it takes the equivalent of two R01s to fund a lab, according to Goodman. And virtually all R01 applications submitted by young researchers are for new grants. So young principal investigators expend large amounts of time on federal and private grant applications that they could be devoting to research.

Gracheva says that grantwriting consumes 30 percent of her 70-hour work week, while Valentina Greco, Ph.D., assistant professor of genetics and dermatology, estimates she writes five or six applications for every grant she receives. “My time goes into writing grants rather than doing science or mentoring my people,” Greco says, “but I must do the grants. I work six times as much so I can cover all my functions.” Applying for grants, says King, takes a good deal of emotional fortitude, and young researchers can’t always look to more seasoned colleagues for guidance: “Even our mentors can’t give us a whole lot of advice, because they’ve never been junior when the NIH was like it is now,” she says.

Recognizing the plight of young investigators, federal agencies have in recent years set aside grants specifically for those in the early stages of their careers. Since 2007, the NIH Director’s New Innovator Award has funded a small number of grants for exceptionally original early-career research, and, by design, the application doesn’t require the volume of preliminary data that the traditional grant system does. Goodman was an awardee in 2012 and King in 2011. And policy changes adopted in 2007 have substantially increased the number and the percentage of R01 awards going to new investigators.

“I am lucky, because there are mechanisms in place to give young, unestablished investigators an edge,” says Jesse Rinehart, Ph.D., assistant professor of cellular and molecular physiology, one of the first scientists to set up a lab at Yale’s West Campus in Orange, Conn. “It’s in the best interest of the NIH and other funding institutions to make sure that we have scientists for the future.”

Despite tough times, the struggle is well worth it, they all agree. Goodman calls it a great privilege to work with his team members, and Greco puts in as many hours as she possibly can. “My job is not my job—it’s my hobby, my passion,” she says. “You just can’t be afraid,” King says. “It is kind of a brave new world, but it’s not hopeless. We’re figuring it out.”