Most high school kids don’t e-mail researchers to ask them detailed questions about their results. But Ethan Perlstein never wanted to be most people. Growing up in South Florida, Perlstein started working in a research lab as a junior in high school and never really stopped. “I always knew I wanted to do science,” he says. That desire led him to undergraduate studies at Columbia University, a doctorate at Harvard University, and a prestigious Lewis-Sigler postdoctoral fellowship at Princeton University.

But as the end of his fellowship approached in late 2012, it became clear that desire, commitment, talent, and a prestigious science education don't guarantee a tenure-track appointment. Despite an impressive pedigree (and a rise to Internet fame in late 2012 when he used RocketHub to fund a "meth lab"), Perlstein couldn’t find a faculty job.

Colleagues told him to try another postdoc or be less selective about where he applied. Neither option was appealing. There was always industry, friends pointed out, but that approach, too, lacked appeal.

So Perlstein did something exceedingly unusual: He struck out completely on his own. As of 1 April, Perlstein is a totally independent scientist.

No one knows for sure exactly how many independent scientists there are, but it’s clear that independent experimentalists are a very rare breed. He announced the transition when it was already under way, on his flight from New York to San Francisco, where he intended to put out his shingle. “I’m embarking on the next phase of my professional evolution as an independent scientist, leaving the Academia-Pharma Complex behind," he wrote in a blog on his lab Web page—another way he had previously won media attention. "I still experience occasional pangs for the professorial fantasy I’d clung to since I was 17, but the withdrawal is gradually giving way to an emboldened optimism,” he continued.

Perlstein tells Science Careers that his decision has been greeted by a wide range of opinion, from “Go get ‘em!” to derision and ridicule. Depending on who he listens to, becoming an independent scientist would appear to be either a cop-out and failure or one of the best ideas that a researcher has had in a very long time. Either way, it is an unorthodox and risky way to cope with the persistent but ever-increasing career-related uncertainties in the biomedical research world.

"Lots of people should be out there, trying new ways of doing science," says Doug Crawford, associate director of QB3, a University of California (UC) biotech research and commercialization institute headquartered in San Francisco. "Ethan Perlstein is exactly the type of person who should be out there doing this."

The problems that Perlstein has had to deal with are familiar. For years, early-career biomedical scientists have bemoaned stagnant National Institutes of Health (NIH) funding, increased competition for those shrinking research dollars, and a declining number of faculty posts. And when scientists do get these jobs, and the major grants that they need to achieve tenure, they are usually in their late 30s and 40s. Henry Bourne, a retired cell biologist from UC San Francisco, calls it the “graying of the professoriate.” “The biomedical research enterprise is currently not sustainable. It’s not going to last in its present form,” Bourne says.

Think of it this way, Perlstein says: “Three hundred to 400 people are applying for one job. Even if only 10 to 20% are serious candidates, you’re still talking about dozens and dozens of candidates who, on paper, look no different than me.” Still, however much the odds may be stacked against him in his current endeavor as an independent scientist, he figures, they probably aren't any worse than they would be if he stuck to the academic track.

Even so, on his current path he faces some considerable—some might say insurmountable—hurdles. His career move means that he now has to grapple with issues for which many scientists don’t give a second thought.

Perlstein brought the yeast strains he developed at Princeton to the West Coast, but left all his lab equipment in New Jersey. He needs everything, from the basics—a PCR machine—to more advanced equipment. The only means he has for paying for that right now is savings and credit cards.

He needs lab space, too, of course. “Until my wife lets me build an experimental man cave next to the house, I’m going to have to find a space to do my work,” Perlstein says. That means renting. QB3's Crawford says that he’s seen an uptick in the number of scientists looking to rent just a lab bench or two, rather than several thousand square feet for an entire lab. “Our business model is that we will rent an individual bench to a startup,” Crawford says. “The demand for this service continues to grow and grow. We now have four laboratory sites and 62 startup incubators renting space.”

Unlike many of the scientists Crawford described at QB3, Perlstein isn’t looking to create a startup company. He just wants to do research and to fund it via a strange mélange that blends the old with the new. Sounding like someone from 18th century Europe, he's looking to locate scientific patrons, one or more people in the Bay Area with some extra cash and an interest in science. Sounding like someone from the 21st century, he plans to try crowd-funding again. He wants to build up a fan base of people willing to chip in small amounts of cash to his research efforts.

“When you’re writing a grant, it’s all about salesmanship,” Perlstein says. Crowd-funding, he says, is the same. “If you take the hustler or entrepreneurial approach, you can raise 25k for basic science research.”

Perlstein has been working with David Sulzer, a neuroscientist at Columbia University, for a little more than a year. Sulzer was involved in Perlstein’s initial “build a meth lab” crowd-funding project. The idea was to use a technique that Perlstein calls evolutionary pharmacology to understand why methamphetamines and other psychotropic drugs, including antidepressants, damage neurons. Experiments (by him and others) with simple model organisms like yeast suggest that the cellular damage is caused by how the cell stores these molecules in fluid-filled sacs called vacuoles. He intends to continue that work in his independent lab.

Instead of looking for large sums of money from one or two places, he sought smaller sums from thousands of people. Selling a scientific idea through Facebook, Twitter, reddit, and so on, isn’t that different from selling your idea on an NIH grant, he says. The popularity of the television show Breaking Bad provided a hook. Many people have personal experiences with the devastation of addiction—including Perlstein himself: Twelve years ago, his mother died after a long battle with mental illness and addiction. His RocketHub campaign raised more than $25,000.

Still, even Sulzer, who is open to the idea of crowd-funding science, points out that it’s likely to be very difficult to fund a lab via crowd-funding alone. “There’s a lot that universities and institutes will support you with that just won’t be there." But maybe there's an upside, too. "On the other hand, can a smaller laboratory do it better by themselves? I don’t know,” Sulzer says.

Perlstein thinks that he's on the vanguard of a movement toward more independent, open-source science. Feedback that he’s received from early-career scientists has reinforced the idea that being independent is the way to go. Even though he has yet to secure lab space or significant funding, he’s beginning to encourage other scientists to think about following his path. It's not as if the conventional route is working especially well.

Practically speaking, Bourne says, it’s unlikely that a significant number of scientists will be able to follow in Perlstein's footsteps. “What Ethan is doing is extremely daring, but it also requires certain things that the vast majority of young scientists just don’t have,” he says. “I don’t know how much money he’s got, but he’s got some. Your average young person beginning in science doesn’t have enough money to take care of his family and fund his work even for a short time.”

Of course there's a chance—it's impossible to accurately set odds—that his venture will be remembered, if at all, as one of the more harebrained schemes that a scientist has attempted lately. He knows that. But, he figures, if he pulls it off, he's a pioneer. If he makes it work, “independent scientist” may soon be as valid a career path as a university professor.

Carrie Arnold is a freelance science writer living in Virginia.
10.1126/science.caredit.a1300107