Home On The Range : Researchers Discover Success In Montana

In the book Shoeless Joe, better known as the movie Field of Dreams, the main character converts an Iowa cornfield into a baseball field after a voice says, "If you build it, he will come." In Great Falls, Mont., supporters of the McLaughlin Research Institute (MRI) began construction of a 42,000 square-foot, state-of-the-art, genetics research facility on prairie farmland in 1991 with the hope that if they built it, scientists would come. The new building, constructed with federal and state funds, was completed in 1993. And the researchers have indeed come, inspired by quality-of-life issues that are making Montana's remoteness attractive. Montana's two state universities and a federal biomedical research laboratory also are experiencing the boon of scientists wanting to seek their fortunes in the state. Just 20 to 30 years ago, scientists who came to Montana ran the risk of jeopardizing their careers. The state's seclusion limited professional contacts with colleagues, and equipment was inferior to those at urban research centers. But those who took the chance now find that advances in telecommunications and changing attitudes toward rural lifestyles have brought once-isolated Montana researchers into the mainstream. Whereas recruiting scientists from within was once a necessary standard practice, now hundreds of applicants vie for each new job opening. Often called the last best place to live, Montana is shaping up as the last best place to practice science, these investigators maintain. "In the information age it is perfectly feasible to run a small, focused research enterprise in a rural setting. You can choose the lifestyle you want and still do first-class research," contends MRI developmental biologist Douglas Coffin. Plus, Montana State University microbiologist Jim Cutler points out, Montana "is a nice place to live." At MRI, recruitment of new scientists has peaked temporarily at four, plus a support staff of 30, even though several hundred qualified scientists have applied. The National Institutes of Health mainly funds the MRI researchers, who must obtain the bulk of their support themselves. Scientists pay standard overhead costs, and MRI provides laboratory space and equipment. SEEKING THE SIMPLE LIFE: Bruce W. Chesebro of NIAID's Rocky Mountain Lab says, "Montana's quality-of-life issues have become a big recruiting tool." These four scientists are four times more than MRI has usually known. The institute was founded in 1954 by pathologist Ernst Eichwald, who recruited the late mouse immunogeneticist Jack Stimpfling from the Jackson Laboratory in Bar Harbor, Maine, in 1964. They ran their laboratory in an abandoned grocery store until 1967, when local philanthropist John L. McLaughlin financed a 4,000-square-foot building. Eichwald left that year to head the pathology department at the University of Utah--where he is now an emeritus professor--and for 20 years, Stimpfling was the sole scientist at MRI. A protèg%egrave; of Nobel laureate George Snell, Stimpfling genetically dissected the H-2 region of the mouse chromosome involved in the immune response and organ transplant rejection. Stimpfling's work comprised 75 scientific papers, and a 1988 issue of International Reviews of Immunology was dedicated to him (J. Klein, Int. Rev. Immunol., 3:291, 1988; T.G. Beito, Int. Rev. Immunol., 3:323, 1988). Stimpfling's lab housed up to 8,000 mice, and genetically altered mice from MRI were shipped worldwide to researchers involved in unraveling the mysteries of the major histocompatibility complex. When Stimpfling retired in 1988, mouse geneticist and MRI scientific director George Carlson came over from the Jackson Laboratory. Today, research at MRI focuses on understanding the genetic basis of normal development and susceptibility to disease. A colony of 10,000 mice serves as the main research tool. MRI's scientific advisory committee includes well-known immunologists Irving Weissman of Stanford University; Leroy Hood of the University of Washington, Seattle; and David Baltimore of the Massachusetts Institute of Technology. Hood grew up in nearby Shelby, Mont., and Weissman is a native of Great Falls. Other areas being studied at the institute include the genetics of neurodegeneration. Scientific director Carlson collaborates with neurologist Stanley Prusiner at the University of California, San Francisco. Prusiner coined the term "prion" to describe novel infectious proteins that do not contain nucleic acids, and received the Lasker Award in 1994 for his discoveries. Carlson, Prusiner, and others use transgenic mice to study the prion disorder scrapie, a naturally occurring, infectious degenerative brain disease of sheep (G. Carlson et al, Proceedings of the National Academy of Sciences, 91:5690-4, 1994). Carlson and his colleagues also developed transgenic mice that mimic features of Alzheimer's disease. The large mouse colony makes MRI "an ideal environment for identifying the genes influencing different disease manifestations," Carlson notes. Developmental biologist William Crain, who relocated from Massachusetts' Worcester Foundation for Experimental Biology in April 1993, studies gene expression in early mouse embryos. Solving such riddles as when after fertilization male sex is determined and the genes involved could aid animal breeders and shed light on birth defects and cancer. Coffin, who arrived in August 1993 from the University of Cincinnati, focuses on genes that regulate the growth of blood vessels (J.D. Coffin, Cell, in press). Controlling these genes could prevent the spread of cancer cells or create new blood vessels to replace those damaged by heart disease or diabetes. The newest institute member, John Mercer, a mouse geneticist who studies kinesins, or unconventional myosins, came in June 1995 from the University of Texas Southwestern Medical Center in Dallas. With a population of 50,000 people, Great Falls seems an unlikely place to build a modern laboratory dedicated to basic research. The city's largest employer is Malmstrom Air Force Base, where 4,500 people work. The state has no medical school and few high-tech industries, and its two universities lie about 200 miles south or east of Great Falls. Of the state's 750,000 people, 113 are members of the American Association for the Advancement of Science. Surprisingly, the location and isolation helped recruit the new MRI staff. "People who could never leave Manhattan wouldn't be interested in this," remarks Carlson, but overall "Montana has been an asset." Montana's big sky and landscape that outruns the vision seduced Crain during his first visit to Great Falls. But back in Worcester, his colleagues told him that moving to Montana was the craziest thing they ever heard, and that science can't be done away from an urban area. The fantasy of working in Montana drew Crain anyway. "To be honest, I don't miss a thing," he says. His wife, Barbara Crain, former library director at the Worcester Foundation, works as MRI's medical librarian. A few applicants have been eliminated early in the recruiting process, acknowledges Carlson, because a spouse could not find career opportunities in, for instance, academic medicine. When Coffin told his colleagues about moving to Great Falls, they asked, "Montana? Why not San Francisco, New York City, Seattle, or Houston?" The lack of crime, pollution, and traffic lured Coffin, his art teacher wife, and young children. Just three homicides and 40 robberies were reported in Great Falls in 1994. Coffin's round-trip work commute takes 15 minutes. In contrast to the large bureaucracies the scientists left behind, MRI has no administrators. Nonscientific employees are called scientific support staff and perform administrative-like duties. Eliminating administrative terminology prevents a class structure and disproportionate lines of power. Because all staff members work to keep costs down, a scientist's ever-dwindling research funds stretch further. "Here I'm paying one-fifth what I paid in Dallas for mice," says Mercer. These MRI researchers came willingly, inspired by a better working and living environment. Not long ago, however, recruiting scientists to Montana was not so easy, recalls retrovirologist Bruce Chesebro, who came 20 years ago to work at Rocky Mountain Laboratory (RML) in Hamilton, Mont. The 75-year-old RML is a branch of the National Institute of Allergy and Infectious Diseases (NIAID), established to study Rocky Mountain spotted fever. Its staff of 120 focuses on infectious diseases. In the 1970s, RML had difficulty recruiting young scientists "because they were afraid it would hurt their careers to come here," remembers Chesebro, who is also a member of MRI's scientific advisory committee. But in the last 10 years, "Montana's quality-of-life issues have become a big recruiting tool." Now "it's easier to recruit people to come here than it is to [NIAID headquarters in] Bethesda, Md.," he says. RML constitutes four departments under the direction of NIAID's Division of Intramural Research. Chesebro, director of the Laboratory of Persistent and Viral Diseases, explores persistent virus infections of the hemopoietic, lymphoid, and central nervous systems; HIV; scrapie; and mouse retroviruses that cause leukemia. WESTWARD, HO: McLaughlin Institute scientific director George Carlson came to Montana from the Jackson Laboratory. The Laboratory of Intracellular Parasites studies infectious diseases caused by intracellular bacteria, such as Chlamydia trachomatis and Rickettsia rickettsii. Animal models help to define the pathogenesis of the diseases and immunological responses of the host. Borrelia burgdorferi, the microorganism that causes Lyme disease, was discovered by and named after microbiologist William Burgdorfer at RML's Laboratory of Microbial Structure and Function (W. Burgdorfer, Clinical Dermatology, 11[3]:335-8, 1993). Neisseria gonorrhoeae and HIV are also investigated, with special emphasis on the genetic events that underlie expression of microbial surface components. In the Laboratory of Vectors and Pathogens, researchers look at similar microorganisms with the goal of producing improved diagnostic tools or vaccines directed against them. Microbiologist Jim Cutler came to RML as a postdoctoral fellow in 1972, then accepted a faculty position two years later at Montana State University (MSU) in Bozeman, where he has remained. For 26 years Cutler, now a professor of microbiology, has studied the fungus Candida albicans. He recently confirmed that an antibody response in mice protects them against candidiasis (Y. Han, J.E. Cutler, Infection and Immunity, 63:2714-9, 1995). The role of antibodies in fungal diseases has been unclear; Cutler's discovery opens the door to the development of vaccine treatments for fatal, disseminated fungal infections. Cutler also worried whether staying in Montana would be detrimental to his career. "In the 1970s I felt a little isolated," he says, "but that clearly is not the case anymore." Easing the isolation that Montana scientists once felt are technological advances, such as E-mail, facsimile transmissions, and overnight delivery services, which allow them to communicate daily with colleagues worldwide. In addition, online library services give remote scientists the same access to information as do libraries in sophisticated urban centers. For Cutler, Montana itself turned out to be an asset to his career. His international collaborators worldwide enjoy visiting Bozeman, situated near Yellowstone National Park. "We've actually benefited in that regard," he says. Escaping into the wilderness helps MSU's Gary Strobel, a professor of plant pathology, solve scientific problems. MAKING CONNECTIONS: Montana State's Jim Cutler notes that his international colleagues enjoy visiting nearby Yellowstone National Park. After completing graduate studies at the University of California, Davis, in the early 1960s, Strobel was advised not to go to the unknown MSU in "nowheresville." MSU had such trouble recruiting 30 years ago that most departments were forced to hire from within. This year, a job opening in the chemistry department attracted 300 responses from qualified applicants because "people want to raise families in a peaceful, lovely place," says Strobel. Within this bucolic setting, Strobel has also discovered the raw materials of scientific advancement. Strobel found a bacteria growing on wheat that produces a compound called pseudomycin, which kills fungus. Strobel first used pseudomycin to kill the fungus that caused Dutch elm disease in 1987. Now pseudomycin is proving effective against a growing number of human fungal infections that kill immunosuppressed patients (L. Harrison et al., Journal of General Microbiology, 137:2857-65, 1991). Indianapolis-based Eli Lilly and Co. has licensed the technology to produce new antifungal drugs. Strobel and his colleagues also came upon a fungus that produces the anticancer drug taxol growing on a yew tree in Montana's Glacier National Park (A. Stierle et al., Science, 260:214-6, 1993). Thus far, however, taxol has been harvested from the bark of rare yews, pitting cancer patients against environmentalists. Genetically engineering the fungus to churn out large amounts of taxol can save yews and increase the supply of taxol. Cytoclonal Inc. of Dallas licensed this technology. The inspiration to search yew trees for a fungus came while walking around a favorite mountain lake. "By going into the wilderness, I can formulate a question and unconsciously solve problems," says Strobel. At the University of Montana in Missoula, the three-year-old department of pharmaceutical sciences has had no problems recruiting new faculty. The department's chairman, pharmacologist Vernon Grund, who came in 1992 from the University of Cincinnati, saw "a tremendous amount of opportunity" in Montana. The lack of a medical school meant that "there was room for growth and I could shape programs," he says. The last search for a new faculty member brought in more than 100 applicants, and Grund landed his first choice. Unlike Ohio, where there was fierce competition among scientists at the state's seven medical schools, Montana scientists have a pioneering cooperative spirit, according to Grund. For instance, to help recruit a new member to the department of pharmaceutical sciences, another department donated a $35,000 ultracentrifuge. "We work together more than anyplace I've been," asserts Grund, who predicts that science in Montana will stay "in the pioneering phase for quite a while." Carol Potera is a freelance science writer based in Great Falls, Mont. (The Scientist, Vol:9, #17, pg.1,10 , September 4, 1995) (Copyright © The Scientist, Inc.)

Home On The Range : Researchers Discover Success In Montana

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