Tired Of Fighting For Resources? Set Up Your Own Foundation

Six years ago, neurologist J. William Langston stumbled onto an exciting discovery, a contaminated synthetic heroin that seemed to trigger symptoms of Parkinson's disease. Almost overnight, Langston was thrust into the limelight. Reporters flocked to his office. Foundations invited him to apply for grants. His lab began reporting steady progress in the long struggle toward a cure for Parkinson's, a degenerative disease that affects half a million people in the United States. But success brought problems as well as accolades. First Langston had to find space to carry out his research; then his initial round of grants ran out, and he began to worry about the precarious nature of his funding. So he took the bold step of striking out on his, own. He left the faculty of Stanford University, severed his ties with the Santa Clara Valley Medical Center and, in April, started his own organization, the California Foundation for Parkinson's Disease and Related Disorders, to support his research. Although it's too soon to tell if the foundation will survive and prosper, Langston sees it as a model for other scientists whose research outgrows the ability of their institutions to support it—a problem he suspects will increasingly crop up in rapidly expanding fields such as neuroscience. This problem was outlined last year by David H. Cohen, vice president for research at Northwestern University, in the newsletter of the Society for Neuroscience. For 40 years, Cohen wrote, teaching and research have been intertwined in the United States. Most federal money for basic research goes to universities, where faculty members simultaneously pursue science and train the next generation of researchers. "It's been an enormously successful model," says Cohen. Shrinking Enrollment But now, the felicitous balance between teaching and research may be tilting. Even as research is expanding in areas such as neuroscience, immunology, and genetic engineering, there are signs that university enrollments—and consequently, the number of available research positions—may shrink. Over the long term, of course, fewer current students mean fewer future scientists. But in the short term, the trimming of faculties could result in a surplus of scientists. Three dental schools have already closed, and others are accepting smaller classes, Cohen says, which is a problem because some dental schools support biomedical research. At the same time, applications to medical schools have decreased, and there is talk of smaller classes there as well. Exacerbating the problem, says Cohen, are deteriorating research facilities at universities. If all these trends continue, Cohen wrote, universities will no longer have large enough faculties to do the research that needs to be done. The government might have to change tack, funding or establishing more freestanding research institutes to employ scientists and to continue research at current or expanded levels. And if that happens, Cohen said, research increasingly will be divorced from teaching and the postwar model will have lost some of its power. It hasn't happened yet, says Cohen, but it could. "I wrote that article to call attention to what may develop as a problem," he says. "The real issue is how the federal government will deal with it." Not everyone shares this worry. Paul Jolly, an associate vice president of the Association of American Medical Colleges, says that the number of basic science faculty members grew 5% per year over the 25 years ending in 1986, while research dollars climbed faster—at more than 6% per year. In addition, says Jolly, faculty size isn't determined primarily by the number of students to be taught, but by the amount of research that faculty members are doing. If the number of students declines, therefore, faculty and revenue won't necessarily follow suit. So Langston doesn't know whether he is really on the cutting edge of a new trend in neuroscience, or just a special case. All he knows is that when he tried to follow up on his initial discovery, he wasn't able to do it in the traditional university setting. When all of this began in 1982, Langston was an assistant professor of neurology at Stanford and chairman of neurology at Valley Medical Center, where he had gone to establish the neurology department eight years earlier. Between teaching and tending patients, he had little time for basic research. Then a 42-year-old man came into the emergency room with the classic signs of advanced Parkinson's disease. He was stiff as a mannequin and could barely speak or grab a pencil—essentially "frozen" inside his own body. His 32-year-old girlfriend was in a similar state. Both were much younger than most Parkinson's patients, and both had been injecting synthetic heroin. Clandestine Lab Within a few months, Langston and Stanford biochemist Ian Irwin had determined what caused the symptoms: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, or MPTP, a toxic contaminant of a drug cooked up in a clandestine laboratory. Excited by the discovery, Langston began to search for laboratory space so that he could explore the drug's actions in rodents and primates. He knew that nothing was available at Stanford, a fact that other researchers confirm. "My chairman couldn't get a broom closet at that time, space was so tight," Langston says ruefully. In addition, he says, as a clinician, there wasn't much room for advancement at Stanford. And so in 1985 Langston cut back his county Parkinson's clinic to one day a week and left Stanford to work full-time at the Institute for Medical Research, a small, independent institute on the grounds of Valley Medical. Founded in 1963 by a group of doctors who wanted to do research, the institute was available to any physician. It had plenty of room and an enthusiastic director. But two years after he arrived, Langston concluded that the institute was not the answer. His initial round of grants, which had brought in $500,000 per year, and which paid his salary, was starting to expire. And as he scrambled to bring in more money, Langston—who had three young children and a wife starting a residency in opthalmology—grew nervous. The institute provided no salaries or other funding—nothing to sustain his laboratory through the inevitable gaps between one grant and the next. "We had jumped off the end of the boat with a three-year life preserver," Langston says. "And after the second year, we looked around and said, 'What are we going to do?' We were deeply vulnerable. I don't think anyone can live on grants alone these days and be happy. It's just too much of a roller coaster." So, early this year he started his own funding organization, the California Foundation for Parkinson's Disease and Related Disorders, which he hopes will provide steady support for his work. In creating the foundation, Langston took as his guide a report by consultant Judy Dudley, who visited a number of independent research institutes, in California last year to see what made them work. Among the successful ones, she found, some were attached to university medical schools. Others, such as the Salk Institute in San Diego, focused on a narrow range of research and had a strong sense of direction. All shared two things: periodic reviews of their programs by outside experts to ensure that the quality of research stays high; and strong, charismatic leadership, both on their staffs and on their boards, Dudley said. In addition, a foundation that tackles a 'major disease has a natural base of support, says Langston. "You have a group of highly interested parties—people who have the disease and their families." Langston believes a strong board is vital, contributing not only business know-how but also community contacts. His board so far includes several business people, an accountant, and a Silicon Valley entrepreneur. In fact, it was a future board member named Jim Bottomley, the owner of a beer-distributing business, who first came up with the idea for the foundation. Bottomley had a personal interest in the research; his father had Parkinson's disease and was a patient in Langston's clinic. Bottomley was about to donate $25,000 to Langston's laboratory when he had a better idea. "I said, 'Well, why don't we start a foundation? That way we can get our own funds,' "he recalls. Bottomley helped recruit other businessmen as board members and found a 5,000-square-foot suite in an office building near Valley Medical for a bargain price. The offices now contain the foundation offices and a clinic, where Langston and a second neurologist currently see Parkinson's patients five days a week and do clinical research. The foundation also plans to offer a room in the clinic to the local Parkinson's support group, which is providing volunteer help. Other supporters have donated paintings for the walls and even a car. Basic research still takes place at the Institute for Medical Research, where Langston's laboratories have expanded into his former office. Once again, Bottomley came to the rescue, hiring a carpenter at his own expense to build counters and insert a doorway. Before, Langston says, "we were just stacked six deep over there. We had small pieces of our lab scattered all over the building. To run an assay, sometimes you had to run around the building two or three times." Now, with the laboratory consolidated and expanded, productivity has greatly increased, he says. Langston now pulls in about $1 million a year in research grants, and he hopes that within a few years the clinic will begin to generate revenue that can be plowed into research. He also plans to hire a professional fund-raiser his dream is to raise a $10 million endowment through public contributions that would give the foundation a steady income. Meanwhile, research continues, bolstered by the addition of a secretary and other support staff. Langston and Irwin work with biologist Lou DeLanney, three postdoctoral researchers, two full-time technicians, and three medical students. The group is trying to unravel the way MPTP acts on the brain. The chemical itself is not the culprit; it is degraded to MPP+, which apparently enters neurons and kills them. (Interestingly, MPP+ has been around for about 20 years; it was originally developed as an herbicide, a chemical cousin of paraquat, which for a time was sprayed by the government to destroy marijuana plants.) The enzyme that turns MPTP into MPP+ is called MAO B. It also oxidizes dopamine, the neurotransmitter whose absence brings on Parkinson's. Some scientists think this oxidation may generate free radicals that in turn destroy nerve cells and trigger symptoms of the disease. Langston's group has been running neck-and-neck with scientists at the National Institutes of Health, the Robert Wood Johnson Medical School in New Jersey, and the University of Rochester in finding this toxic metabolite and reporting its effects in animals. The researchers have all shown that MAO inhibitors can block the development of Parkinson's symptoms in primates exposed to MPTP. Langston is participating in a multicenter clinical study to see if deprenyl, which inhibits the activity of MAO B, can stave off the worst effects of Parkinson's in patients who already show early symptoms. The group continues to test the effects of MPTP and MPP+ on mice and primates, and it has received funding to start a search for similar chemicals that may trigger Parkinsonism. And the team is trying to track down people who took the tainted synthetic heroin. So far, half of the 150 addicts they have evaluated show signs of Parkinson's. 'Tough' Challenge Some observers say the young foundation may have a hard road ahead. "You don't just go build a building and go in there and do research," says Joe D. Coulter, chairman of the anatomy department of the University of Iowa College of Medicine and secretary of the Society for Neuroscience. "It's tough." He says that supporting a group of 15 active researchers, the size of his department, would cost $5 m ion to $10 million a year. Langston is only too aware of the need to raise money along with recruiting board members, it takes up a lot of his time. "I'm beginning to feel like a capitalist," he says. "It's a very different kind of activity than one learns in medical school." The incessant drive for funds also worries some scientists. "It puts scientists in an entrepreneurial position and avoids the peer review system," says Richard E. Heikkila, a Parkinson's researcher at the Robert Wood Johnson Medical School. "But for Langston, I think it will work. He is both very effective out in the public eye and has done some very good work." So far, says Langston, the foundation seems to be succeeding. "There have been major ups and major downs," he says, "but the ups have been sensational—the opportunity to pursue what you want to do, to do pure science, without the burden of teaching and committee meetings. It makes me wonder how lever did it before. It's like having chains removed." And in the end, he considers the foundation a sort of experiment in itself—an example of the type of institute that may increasingly crop up as a result of the conflicting agendas of research and academia. "It will be interesting to see if we're successful," he says. if not, "maybe our failure will teach us something." Glennda Chui is science writer at the San Jose Mercury News, currently on leave as a Knight Fellow at MIT.

Tired Of Fighting For Resources? Set Up Your Own Foundation

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