Sci. Aging Knowl. Environ., 15 May 2002
Don't Pass the Buck
In the hills of Northern California, a community of scientists digs for roots of aging at a novel institute
Abstract: As the first nonprofit center for research on aging in the United States, the Buck Institute for Age Research has broken ground in more ways than one. Housed in designer buildings, an enthusiastic faculty is taking aim at diseases from Parkinson's to cancer and delving into the myriad of processes that might contribute to a creature's demise. Because the institute is only two and a half years old and has just 14 lab heads, it's too soon to tell how big a player the Buck Institute will become in the field of aging. But talented researchers, state-of-the-art technology, and generous institutional funding all bode well for its future.
From Rocky Start to Lofty Goals Back to TopFrom San Francisco, the drive to the Buck Institute for Age Research crosses the Golden Gate Bridge into Marin County. Highway 101 leads north, weaving past malls and housing developments. About 50 kilometers past the bridge, 101 narrows from three to two lanes in each direction; horses and cows replace shopping centers on the surrounding hillsides.
The institute emerges from rolling hills, its white walls shimmering in the distance. The route from highway exit to Buck Road dives farther into the countryside. At the wooden security gate, a voice from the small intercom asks for a name. The buzzer sounds and the gate opens onto a steep drive that winds up the oak- and shrub-lined hill, which allows only an occasional sideways glimpse of the limestone buildings. One feels very far from civilization.
The distance from the city creates many of the institute's inspiring quirks and potential pitfalls. It is at once too isolated--but also beautifully, refreshingly isolated.
I. M. Pei, best known for his glass pyramid addition to Paris's Louvre Museum, designed the two-building geometrical collage. The sweeping walls, sharp lines, and jaunty skylight hat perch above sloping pastureland and grazing cattle. The institute's roots stretch back to 1975, when a Marin County nurse and philanthropist died, leaving her estate to a local foundation with the proviso that it be used to help the people of Marin, including the aged. Now receiving one-third of its operating budget from the Buck Trust, the center is the fledgling victor in an 18-year war of lawsuits that have challenged its location, its affiliation, and the existence of its animal research facilities (see sidebar). The pluck of the designer building suits the place, not only as the survivor of so much opposition, but also as a unique establishment: It's the nation's first private, nonprofit institute for aging-related research.
When its doors finally opened in autumn 1999, the institute turned its attention to establishing its scientific credentials. "In the next 10 to 15 years, I hope and expect we'll become the Salk of aging," says Simon Melov, one of the founding faculty members. At a fifth of its projected size, the Buck Institute is already making a name for itself.
A Research Palace in a Distant Land Back to TopFrom the visitors' parking lot, a curved path leads to the main entrance. Away from prying highway eyes, the Buck Institute opens up; the walls seen from the road border a two-story-high glass entrance. Beyond the doors, the building--which researchers have described as a palace, a museum, a jewel, and a work of art--overwhelms. The pale stone, spare decor, walls of windows, and high ceilings collude to create a structure that seems more roomy than it is. A peek into the 23-meter-high sunlit atrium, which lies to the left of the reception area, adds to the impression of continuous and flowing space and cements the feeling that the place has been delicately crafted by the hand of a talented artist. Clacking footsteps and an occasional murmur of conversation drift back to the foyer, hinting at the activity that goes on just past the hallway or up the stairs.
Before allowing its visitors to peruse the building or admire the vista, however, the Buck Institute takes care of business. First the guest signs in, noting the time of arrival and staff to see. Before leaving, she must sign out, penning her name beneath a paragraph that reads: "Your signature below indicates your agreement to maintain the confidentiality of this meeting at the Buck Institute for Age Research." After supervising the sign-in procedure, a solemn receptionist briskly lifts the phone and calls an escort.
The view from the waiting area through window-walls contrasts with the efficient security. The enveloping hillside makes it easy for visitors to forget, just for a moment, that they're in a high-tech research facility. "I sit up here every day looking out the window," says Buck Institute molecular biologist Julie Andersen. "Driving to work--it's awe-inspiring ... [which] increases the enthusiasm. Being in a place so beautiful and calming makes it a real pleasure to come to work."
Deer, wild turkeys, and green hills somewhat compensate for the 45 minutes it takes to get to the University of California, Berkeley, or UC San Francisco (UCSF)--not including time spent looking for a parking space--but the institute pays a price for this distance. "It's so bloody isolated," says George Martin of the University of Washington, Seattle, chair of the Buck Institute's Scientific Advisory Board. "It's not as easy to interact with other researchers as [it is] on a major campus, where you bump into people from many different disciplines on a daily basis."
For this reason, it's especially important that the Buck Institute forge connections with nearby universities, says Martin. So far, it has formalized a relationship with Lawrence Berkeley National Laboratory (LBNL), which now allows students and staff to do rotations there. Negotiations with UCSF are under way to establish a similar agreement. The Buck Institute has no plans to confer degrees, says director of public affairs Elizabeth Eshoo. Some of the lab heads miss the "energy that comes from scientists just entering the field," says Buck Institute cancer biochemist Michael Ellerby. For now, "the Buck focuses on training postdocs," says molecular biologist Tamara Golden, who came to Melov's lab after earning her doctorate at Johns Hopkins University in Baltimore, Maryland, which makes it a "nice place" for that career step.
Although they would welcome graduate student enthusiasm, many of the institute's researchers don't feel particularly secluded. Half of the laboratory heads have at one time been affiliated with UCSF, so they already have links to the Bay Area scientific community, says Buck Institute neurologist and neuroscientist David Greenberg. And with modern technology, physical distance can be a moot point, adds Martin.
A Growth Attitude Back to TopWith only 14 laboratory heads, the Buck Institute has yet to reach the critical mass that makes for dynamic research, according to Martin. "It's terribly important, especially for young people, to have neighbors doing outstanding science with whom you can interact and [from whom you can] learn," he says.
To overcome the limitations of a small population, the Buck Institute must "grow fast and intensely," says Judith Campisi, a cell and molecular biologist at LBNL, who began a part-time appointment at the institute in March. She cites New York state's Cold Spring Harbor Laboratory, a first-class research institution somewhat distant from a major university, as an example to follow. Similar in size to what is projected for the Buck Institute, the laboratory has thrived on Long Island by nurturing diverse and successful research programs, hosting weekly talks, maintaining a relationship with a local university, and establishing an in-house program that awards doctoral degrees.
Weekly seminars bring staff and scientists together with those from local institutions to hear investigators from around the world, adding to the institute's functional bulk. The talks have hooked up Golden, one of the few postdocs studying basic mechanisms of aging, with other researchers who are doing related work. "We've had so many great speakers," Golden says. "There are lots of opportunities to meet people on the forefront of aging research."
And the Buck Institute plans to grow. CEO Dale Bredesen, a neurobiologist who has helped shape the place since its inception, aims to build a first-class research institution, with enough scientists to foster provocative intellectual interactions. Staff size will reach 550, with 450 researchers, 45 group leaders, and additional support personnel. Right now, the workforce is limited by the number of available lab benches: The two current buildings are nearly full. Three more are planned, one of which should be built in 4 years, Bredesen says, with the other two ready for research in ten.
Space is scarce, but interest abounds. "I keep hearing from young people eager to go there," Martin says. Melov agrees that the Buck Institute will easily find good people: "We're having trouble beating off potential applicants."
Many factors are enticing researchers, according to scientists at the institute and others familiar with it. Clinical, teaching, and administrative commitments at universities usurp time many investigators would rather spend on experiments; such obligations are practically nonexistent at the Buck Institute. The quality of research also draws potential hires. And the opportunity to work at a place that focuses on aging forms the centerpiece in this triptych of principal motivations.
Young and Powerful Back to TopEvery palace has its dungeon--but the Buck Institute's institutional white, windowless underground floor houses state-of-the-art vibration-sensitive equipment rather than torture chambers. In a long, rectangular office sits Paul Goldsmith, director of the morphology core, one of three centralized technology facilities. Goldsmith runs in-house imaging and builds whimsical mobiles on the side. He talks about both with equal parts enthusiasm and goofy puns. One mobile is composed of umbrella struts, promo Internet discs and found twist-ties. The title is posted on a file cabinet by the wall: See Deze Pretty Seedy CD's.
As for imaging, he says he's excited by the challenge of figuring out how best to get a picture of what the researcher needs to see. The core's motto, he says, is the adage "The difficult we do right away; the impossible takes a little longer."
Investigators can take advantage of the core facilities--morphology, genomics, and proteomics--without having to invest in their own equipment. Such a setup is rare among nonprofit institutions and universities, where cost and institutional barriers often stand in the way of such cooperation. An experienced staff runs the facilities and helps investigators use the equipment and interpret results.
The core facilities drew Vivian Hook from UC San Diego to the Buck Institute. Hook's research focuses on the relation between aging and neurodegenerative diseases. She is especially interested in the role of proteases, scissorlike enzymes that cut up proteins and have been linked to the development of Alzheimer's and Huntington's diseases. Hook, who retains her university affiliation, says she hopes to find other rogue proteases, a task the institute should facilitate. "The best science has to use all the newest technology," she says. "All the cores here--genomics, proteomics, morphology--need to be used together to solve problems."
Two floors up, Mark Eshoo directs the genomics core. Eshoo has developed technology to help researchers compare gene activity in different types of cells--healthy and diseased, for example. Sophisticated robotic machines dispense samples of thousands of individual genes onto treated glass slides, creating microarrays that are specialized for studying aging and age-related diseases. Through methodical experimentation, Eshoo and his team have worked to make each step of the process as efficient as possible, allowing researchers to generate reliable data from very small tissue samples. They're even refining the size and spacing of drops of genes on each microarray. "Perfect little spots are very important," Eshoo says with a laugh. "There are nights I close my eyes and see perfect little spots."
The proteomics core, led by Bradford Gibson, who remains an adjunct professor at UCSF, also resides upstairs in immaculate rooms. The Buck Institute is ideal for his mass-spectrometry work with minute concentrations of substances, he says: "I couldn't do it in my lab at UCSF because it wasn't clean enough."
The atmosphere has affected more than the precision of his research. Gibson, Eshoo, and Goldsmith are new recruits to the field of aging. "They came here because they had the technology the rest of us were interested in," says Andersen. "And now they are interested in applying it to aging."
A Bubbling, Diverse Community Back to TopThe Buck Institute has succeeded in luring scientists with varied backgrounds. Ellerby came with Bredesen from the Burnham Institute in La Jolla, which specializes in basic research on cancer and age-related diseases. There he developed proteins that take aim at the vessels that deliver blood to tumors. Now he investigates how these proteins, called hunter-killer peptides, kill cells. He also hopes to perfect the peptides for future use as a cancer treatment. The new environs have inspired him to start a project investigating basic mechanisms of aging using Caenorhabditis elegans. Institutional funds that supplement grants make it easier to shift focus than if researchers had to apply for money to launch work from scratch. The extra support also allows them to go off on creative tangents, Ellerby says.
If a Buck Institute researcher wants to move into a different area of aging-related research, resident investigators with far-ranging expertise can give advice. Ellerby says that the faculty is creating a previously underexploited midpoint between a place with a very specific focus--such as the Parkinson's Institute in Sunnyvale, California--and one with a broad range of research programs, such as a university biology department. "Being around people who are complementary but not redundant encourages my head to be free, to start thinking way outside the box," he says. Researchers are studying a variety of subjects, including some, such as cancer, that might not be considered aging-related in other contexts, says Gordon Lithgow, who relocated from the University of Manchester, U.K., in July. "At one end of the spectrum you've got basic biology, and at the other end of the spectrum you've got ... age-related diseases."
Currently, Lithgow, Melov, and Campisi run the only labs focusing on fundamental mechanisms of aging. Bredesen, Melov, and others say that this situation will change--and researchers from outside the institute agree that it should change to promote invaluable interplay between the two factions, basic biological and disease-related research. "It's like a pair of horses pulling a cart," says Thomas Kirkwood, a gerontologist at the University of Newcastle, U.K. "You need to have them pulling together."
Being around investigators who study different aspects of aging has led Lithgow's lab to consider new directions. "Now, we are side by side with people interested in age-related diseases, and we're forced to think about the meaning of basic biology in that context," Lithgow says. He's already spawned a new collaboration with Gibson and molecular endocrinologist Matthew Gill to identify hormones involved in life-span determination and is discussing additional possibilities with several other investigators.
Small Town, Big Science Back to TopAt the Buck Institute, everyone knows everyone. It has a "tight-knit sense of community, a small-town feel," Andersen says. For more than a year, the offices lacked name plaques. Even now, those who have them acquired them informally, says Lithgow--as gifts, for example.
It's a village with young families. Five women gave birth within just a few months in summer 2001. Two of the new mothers work in external affairs and are the spouses of other staff members (Mark Eshoo and Simon Melov). Among the ranks of the lab heads are two couples: Michael and Lisa Ellerby and the recently married Julie Andersen and Gordon Lithgow. A few more couples among the postdocs add to the mix. Positions for both Andersen and her new husband were "definite advantages" when they were looking for a place to set up shop, Andersen says.
Like a small town, the Buck Institute feels a bit insular; strangers are looked upon coolly, and the atmosphere is more constrained than at the average university. A press officer chaperoned five of the 13 interviews I conducted for this story, and visitors must make appointments. Limits on public access are solely out of concern for the investigators, says Elizabeth Eshoo. The goal is to protect their research from unwanted and potentially detrimental disruption. "It would be highly impractical to have people wandering in and out of labs," she says.
Other features distinguish the institute from both universities and companies. Researchers have a lot of input, for example. "I tried to set this up as an institution of scientists, by scientists, and for scientists," says Bredesen. "The only research directive is to work on something somehow related to aging, a very loose term in itself. In my opinion, some institutes have far too much input from the administration." Lithgow adds: "There's a real esprit de corps, with people saying Let's make this place as special as we expect it to be."
After all, the Buck Institute is a start-up--it's new to this business. "Not many opportunities come along to be on the ground floor of a research institution," Gibson says. "To develop a whole new culture and scientific interaction seemed exciting." Right now, onlookers are still waiting to see how the center will turn out. Although researchers in the field of aging know the Buck Institute, its name doesn't yet carry the recognition of some of the major Bay Area universities. Neurobiologist Rammohan Rao mentioned the institute to his dental hygienist, who wondered whether it was dedicated to the conservation of deer.
But the institute's researchers are nudging it into the limelight. Melov and Lithgow published a paper in the 1 September 2000 issue of Science showing that a free radical-attacking drug lengthens the life-span of C. elegans. Such high-profile studies demonstrate that, in the scientific world, the institute is ready for prime time. As additional reports appear in prestigious journals, Martin says, the Buck Institute's name will become more widely familiar.
Researchers within and outside the young institute seem optimistic about its potential to become a powerful player in the field of aging, although all admit that it is too soon to tell how it will shape up. New recruit Patrick Kaminker, a cell and molecular biologist who came from LBNL with Campisi, sums up the attitude of many. "I'm hesitant but excited," he said just before making the move. "It's a new facility. It still has to grow and cement itself in the field, but it has a lot of potential."
What is clear already is that the Buck Institute, like other research institutions, will be evaluated by productivity and by who works there. As it builds labs, adds staff, and capitalizes on its youthful exuberance and technical resources, it might well carve its niche in the vast landscape of aging-related research. The energy of its scientists seems likely to fuel its success and prove that a vibrant research facility can thrive on its idyllic Northern California hillside, far from the hustle and bustle.
May 15, 2002
Solana Pyne is a science writer in New York City. She, too, would like to have more space.
Science of Aging Knowledge Environment. ISSN 1539-6150