Brave New World

The Janelia Farm Research Center in Loudoun County is state-of-the-art and so well funded that its scientists can concentrate on what they do best: thinking.

Off Route 7 in Loudoun County, about 35 miles from Washington, D.C., a striking white building sits in the middle of Piedmont farmland, its modern architecture in sharp contrast to the historic Tudor manor that overlooks the property. Inside this elongated contemporary building is a one-of-a-kind science research institute. Opened only two years ago, the Janelia Farm Research Campus is said to be at the forefront of brain research in the world, and the ambitious officials who manage the center say they hope to one day decode the mysteries behind such diseases as muscular dystrophy and Alzheimer’s.

What makes this research center unique, perhaps even extraordinary, is that it is completely independent of the government and the overarching bureaucracy of the National Institutes of Health—a chief source of funding for scientific research in the U.S. Janelia Farm gets no federal funding and has no affiliation with the NIH. It is part of the large and extremely wealthy Howard Hughes Medical Institute (HHMI), which comprises more than 300 researchers at 67 universities throughout the United States. It is the second-largest nonprofit foundation in North America, with an endowment of about $18 billion.

That kind of financial cushion gives Janelia Farm researchers, and those at other HHMI facilities, an autonomy that other research organizations can only envy. They are not weighed down by the 30-page grant requests, peer review processes and short-term performance pressures associated with the NIH. And with an annual operating budget of $80 million, Janelia researchers can push the bounds of knowledge in some of the most important areas of biomedical research.

“We made a decision to not take any [federal] funding for two reasons,” says Gerald Rubin, vice president and director of the Janelia Farm Research Campus and a former HHMI investigator at the University of California, Berkeley. “First, we are fortunate to have a large endowment. Second, we want to fund more risky [approaches] that have a great chance of failure—but that, were they to succeed, would lead to much greater advancements.” That approach is problematic when applying for government grants, because grant-approval committees “are conservative [and] they tend to not fund risky things.”

Research at Janelia Farm is divided into two main fields. The first is the development of higher-resolution imaging capabilities to allow scientists to better study cellular structures. This is done in two ways—by modifying computer programs to better process what is seen through microscopes, and by manipulating the organisms they are viewing to allow for a better image. The second field is neuroscience, specifically brain research in smaller animals such as fruit flies and mice. There are six research teams currently working on neuroscience projects, a total of 13 visiting and lead scientists and a number of post-doctoral students.

According to Rubin, most of the research currently being performed at the center will not have practical applications for perhaps 50 years. Everybody understands that: The Janelia ethos is to branch out, to extend the experimental reach, and then to see what emerges. This open-ended approach is different from the mentality of both the NIH and major pharmaceutical firms where, for the most part, only projects with the potential for a quick payoff gain funding. Even research at major universities is constrained by governmental oversight.

Researchers at Janelia say that the greater intellectual freedom is the main reason they work there. Robert Singer, a visiting scientist from the Albert Einstein College of Medicine in New York City, travels to Janelia about six times a year to work on a microscope project concerning gene activity within a cell. “If you are the professor at a university, you have a lot of other different things going on, fires to put out,” says Singer. “I really enjoy going out to Janelia because all of that disappears. While I’m there I can clear my head.”

The Albert Einstein College of Medicine, where Singer teaches full time, receives $150 million annually in NIH grant money. But there is red tape attached to it. “At a university, you have lots of duties; you have to write grants to get money,” says Singer. “That is one of the biggest energy expenditures. You get rid of a lot of that baggage at Janelia.”

Indeed, Janelia researchers are removed from just about everything but science. The daily errands that yank employees away from their offices are not a bother at Janelia, whose staff takes care of such quotidian tasks as dropping off and picking up dry cleaning for the scientists, and providing on-site day care. “I think Janelia is a brain-freeing environment,” says Singer. “You can think about things in depth. At other places, an amazingly small amount of time—only a few minutes each day—is spent really thinking.”

Janelia Farm is an equal-opportunity brain trust. The center invites scientists from around the country, and the world, to spend time at its facilities. Last year, more than 20 scientists from Germany, France and England worked as investigators at Janelia, on projects ranging in duration from two weeks to a year or more. What’s more, Janelia holds about 15 conferences annually, and on average 20 percent of the attendees come from foreign countries.

This collaborative philosophy is at the heart of the enterprise. Ground was broken on Janelia Farm in 2000. The HHMI had paid $53.7 million for the 281 acres in Ashburn in December 2000, with help from a large and controversial county tax break awarded in the hope that the center’s presence would attract more biotech to northern Virginia. Janelia Farm was officially opened October 5, 2006. The month before, the center had hosted an international conference with top biomedical scientists from 28 countries, who discussed some of the biggest medical challenges of our time: tuberculosis, malaria and antibiotic resistance.

The architecture of the building, designed by award-winning architect Rafael Vinoly, is a Jetsons-esque open glass and metal design, a stark departure from the nearby historic manor and farm that give the research center its name. The centerpiece of the complex is the 1,000-foot-long Landscape Building. All of its architecture is open; the bottom floor is a snaking atrium that, with all the landscaping, offers niches and nooks for meetings and luncheons. Even the labs and offices on upper floors have few fixed walls. Researchers doing completely disparate work might be next to each other, separated only by modular walls—and all of the labs can be reconfigured in a matter of hours, if necessary. In addition to the Landscape Building, there is a conference center, a 96-room hotel to house visiting scientists, and 36 two-bedroom apartments for permanent scientists.

Janelia, then, is a place quite unlike the real world. “In universities, scientists are in different departments, and the idea of physicists and biologists getting together to make a new microscope doesn’t go well,” explains Rubin. “There are types of science that don’t flourish there. But here there is more interdisciplinary research. [We have] no departments. We recruit physicists who want to work with biologists. We recruit people who wouldn’t fit into a typical university structure.”

So far, the collaborative philosophy seems to be paying off. Last March, a research team at Janelia led by Jeffrey C. Magee discovered, through their work with rats, a new way that neurons can store information in the brain. Their results were published in the venerable Nature magazine. The next step for Magee’s team will be to study how environmental changes—say, the addition of new toys or new rats to a community—might affect how the animals process information. These discoveries will lay the foundation for determining the mechanics of human brain activity, particularly memory, a key component to understanding, and one day alleviating, diseases like Alzheimer’s.

Though any practical payoffs from this neural research are far off, the potential effects could be tremendous. And that’s just how Janelia Farm wants it. “We think this type of [long-term] research has been downplayed in government, where scientists typically get five- to seven-year grants,” says Rubin. He says that in Janelia’s earliest days, he and others tried to look out over the scientific horizon, the next 10 or 20 years, and ascertain what key medical challenges loomed. “We asked, ‘What are our scientific problems? What are the questions not being asked in universities?’ From that we set our goals.”

Many of Janelia’s operating principles were inspired by legendary laboratories. In the 1970s, Rubin studied at Cambridge, at a lab called the Medical Research Council Laboratory of Medical Biology (MRC-LMB). There, he did postdoctoral work studying DNA, in some of the earliest human genome and gene organization research in the world, and rubbed elbows with such luminaries as James Watson and Francis Crick. Like the famous Bell Lab, the renowned laboratory whose scientists won six Nobel prizes, invented the transistor and pioneered C++ programming and the UNIX operating systems, the MRC-LMB had a loose, ad hoc structure. There were no prerequisite courses, and younger scientists worked in smaller groups and then took counsel from the older more experienced researchers. When Rubin became director of the Janelia research campus in 2003, he incorporated the same ideas into the venture’s mission, philosophy and operating system.

The overarching mission of HHMI was established 50 years ago, when enigmatic, reclusive billionaire Howard Hughes, created HHMI as a tax shelter in the waning years of his life. Hughes gave the foundation an ambiguous mission statement: that its money must be used for “the promotion of human knowledge within the field of basic sciences,” which should “probe the genesis of life itself.” Hughes died intestate, so after several years of legal wrangling, the organization was finally granted $5 billion in 1984.

With that as seed money, the HHMI grew steadily over the next 20 years, and today only the Bill and Melinda Gates Foundation has a larger endowment. Hughes is also the second-richest medical research foundation in the world, after the British Wellcome Trust. Former HHMI president Thomas Cech estimates that the institute spends on average about $1 million per year per investigator, or about $450 million in total operating expenditure per year.

This economic self-sufficiency is a rare thing for scientists. “Janelia has the resources to get what you want to get,” says Singer. “The instruments we use are very expensive—some about half-a-million dollars apiece. Usually you have to write a grant to NIH, and in a year you have your instrument. There is none of the bureaucracy of the NIH to go through at Janelia. Here, you ask someone, tell them it is important to the project and they say, ‘Here you go,’ and that’s that.”

Scientists at Janelia also escape the committees and teaching requirements that are part of university research. David Clayton was a researcher and professor at Stanford for two decades before coming to HHMI as a senior scientific officer in 1996. He now works at Janelia heading research into the functions of mitochondria within cells. While he loved Stanford, Clayton says, “You can find yourself sitting on more committees than is good for your health.”

Sean Eddy, a Janelia investigator working on DNA sequences and a former associate professor at Washington University School of Medicine in St. Louis, agrees. “I like to work with my own hands on hard problems,” he says, “but science at a modern university means a guy with my experience level must be a full-time manager of a team of junior people, who do all the experiments. That isn’t much fun for me.” Eddy notes that such a hierarchical structure “limits the difficulty of the problems you can tackle.”

Right now, Janelia is focused on expanding its elite corps of researchers. The center employs 300 now and aims to double that number in three years. “We are halfway through a five-year process of hiring,” says Rubin. “We need to fill the buildings.” The hiring process at HHMI’s research centers is rigorous. All current Janelia researchers have Ph.D.’s from the top-ranked scientific or academic institutions in America and abroad.

“The main thing,” says Clayton, “is that this is really a major new venture in American science. There is the excitement of being new. There is a vitality of having a large number of younger scientists, and this is contagious, I think. To a large extent, it’s a protected environment in terms of doing science—no lag time. If you’ve got an idea, you can really make it happen quickly.”

Looking ahead, all the foundation money and innovative planning in the world may not accomplish much unless America can start turning out more scientists. We have a dearth of basic science researchers, and experts say it’s a crucial problem.

To help fix it, Janelia has organized a five-year program, with $22.5 million in financing, to spark interest in science as a career among high school and undergraduate students.The Science Education Alliance Program, as the program is called, seeks to introduce undergrads to hands-on laboratory research, which, unlike bookwork, is the exciting end of the research business. The program was launched in the fall of 2007 at the University of Pittsburgh, and 12 additional universities are participating in the project this year.

Nobody knows what sort of breakthroughs Janelia’s scientists might make in the future, but everybody at the new facility is excited about the possibilities. “You can’t predict when you will learn something,” says Clayton. “You don’t know when you will make a big discovery.”

Adds Rubin, “Biology has made tremendous progress in the last 20 years in DNA, in genetics. Yet, how the brain works is still the great mystery. This will be key for biologists moving forward. Maybe in the next hundred years we will have some answers.” It’s almost certain that we will, and maybe some of them will come from the smart people working at a modernist research center in northern Virginia.

– Originally published February 2009

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