Dr. J. William Langston, who was then the chairman of neurology at Santa Clara Valley Medical Center, tried to help solve the mystery. Parkinson's normally attacks the elderly, and its symptoms develop over a long period of time. Nothing about this young man's affliction made

any sense, until one day, the team achieved a major breakthrough.

"He couldn't speak, so we asked him to write. At one point, we asked him if he was on any medication," Langston says. "He finally wrote out 'heroin.'"

What resulted from that moment was a major leap in Parkinson's research—and the development of one of the world's most comprehensive treatment and research facilities for the disease. That case was the first indication that Parkinson's might be caused by the environment.

The Parkinson's Institute has an international reputation and relationships with some of the more famous faces of Parkinson's, including Michael J. Fox and Muhammad Ali, but it's housed in an ordinary, two-story office building in north Sunnyvale. While not well known on a local level, the institute is branching out, with a bill soon slated to pass through the California Assembly that could provide invaluable data for the study of Parkinson's.

But all the efforts that the institute have made started back with that one patient more than 20 years ago. "The institute began with a medical detective story that's now famous in the annals of medicine," Langston says.

Through media exposure, Langston and his colleagues came across several identical cases of young heroin addicts in Northern California who basically developed full-blown Parkinson's at an extremely accelerated rate. Comparing their stories pinpointed one common factor—a house in Morgan Hill that produced a batch of tainted synthetic heroin.

"Instead of making heroin, they made one of the most selective brain toxins that we know of," Langston says.

This case provided enormous clues into the way Parkinson's disease develops and led Langston to later identify a molecule called MPTP, also called 1-methyl-4-phenyl-1,2,3,6—tetrahydropyridine, which is essentially the chemical that affects the area of the brain that has long been known as the key site for Parkinson's. This case and the research that stemmed from it were reported in a number of science and medical journals and written into a book titled The Case of the Frozen Addicts, which Langston co-authored with writer Jon Palfreman.

But the ensuing research on Parkinson's took a while to fully develop. Langston, who attended medical school at the University of Missouri, initially came to the Bay Area to intern in the neurology department at Stanford University. He came on board at Valley Medical Center in its early days and helped found its neurology department. Langston was working at Valley Medical and as a faculty member at the Stanford medical school when he came across the afflicted heroin addict.

"There was no good model before, so that caused a revolution in research," he says. The discovery indicated that environmental factors were key in the development of Parkinson's. Langston began researching while he was still on staff at Valley Medical Center and treating patients with a number of neurological conditions and movement disorders like Parkinson's. With the encouragement of his friend and mentor, the late San Jose businessman Jim Bottomley, Langston eventually formed the institute in 1988.

"In a thousand years, I never would have thought of that," Langston says, touting his lack of business experience. "I didn't even know what a W-2 form was."

The early days of the institute were held in a trailer right near Valley Medical Center. Langston says the unsophisticated site sometimes proved challenging—there was a bus stop right outside the trailer, and a dog pound nearby. Every time a bus rumbled past, a huge number of dogs started barking.

The research side of the institute took off quickly, but a number of his patients from Valley Medical Center insisted upon continuing treatment with him, leading to the formation of the clinic that's still part of the institute today. "We set up a comprehensive center—care, clinical research and patient research all in the same place," he says. "We're basically a microcosm of Parkinson's research."

The institute's clinic treats movement disorders such as Parkinson's disease and Tourette's syndrome with drugs and physical therapy. The clinic supplies patients for the institute's research. Their clinical research department searches for a cure through drug trials and other physical procedures. But many of the goings-on at the institute are taking place in the field of patient research, which examines a patient's background.

Langston says epidemiology—the study of the patterns of disease in humans—has shed a lot of light over the past 16 years on how Parkinson's develops. Much like an early epidemiological study that pinpointed a single London well as the source of that city's cholera and typhoid outbreaks, the institute's research has examined the development of Parkinson's in twins who served in World War II as well as in agricultural workers.

The results of these studies have shown that genetics likely do not play a huge factor in the development of Parkinson's. "We've seen a lot of hints, but no smoking gun," Langston says. There are certain types of fertilizers used in organic farming and that appear in nature—including one called rotenone that has induced a Parkinson's-like disorder in rats—that might be implicated in some Parkinson's cases. Other research shows that heavy exposure to metals could induce Parkinson's. Many of these discoveries were possible because of the resources at the institute.

"There are hundreds of research projects that die in the laboratory," Langston says. "At a university, a guy in a lab makes a discovery, but it could be months before he gets to speak to a department head to go to the next step. Having everything under one roof and working for one cause is seamless. We can easily move back and forth from bench to bedside."

This comprehensive approach has garnered the institute's members accolades from many of their colleagues. "They are one of the leading institutions in the country focused on Parkinson's. They put together all the parts of the puzzle, and they've done a very good job," says Dr. William Mobley, head of the Stanford Brain Research Institute. "I'm not sure there's another freestanding institution that brings everything together like they do."

Langston has won awards from groups such as the New York Academy of Sciences, the Parkinson's Disease Foundation and the American Academy of Neurology. He also serves on the scientific advisory committee for the Michael J. Fox Foundation for Parkinson's Research and flies to New York at least once a month to consult with the group.

The acclaim has come in handy when fundraising. Langston says the early years were tough, but as the institute's research has grown, grants have come flooding in. The twins study was the result of a $3 million grant, and the institute holds regular galas and solicits donations from contributors. Corporations also contract out studies with the institute. But then, "our ship came home two years ago," Langston says.

Dr. Ken Olden, the director of the National Institute of Environmental Health Sciences, visited the institute to examine their research, and came away with the conclusion that the environment does play a major role in the development of Parkinson's. As a result, the institute was one of three centers to benefit from a $20 million grant from the National Institutes of Health in August 2002 to examine those environmental factors.

This grant has helped set the tone for what Langston now calls "one of the most successful times for research." A number of projects are under way in various corners of Parkinson's research, studying everything from the effects of MPTP in animals to cell and tissue replacement therapy. The use of fetal tissue was banned under the administration of the first George Bush, but studies that transplanted such tissue into the human brain got going when President Clinton's administration reversed the ban.

According to Langston, those studies were completed two years ago and showed that particular technique didn't work. But he's still encouraged by the idea and others that didn't always work on the first try. "The way they did it didn't work, but in some ways, it's like building a house and going in to rewire it. It's not easy to do," Langston says. "I'd really like to see us find the cause or a cure before I retire." He says he wants to see the restoration of the use of stem cells, banned under the current President Bush, to help replace deadened brain cells in a procedure called neural grafting.

One of the "hot theories" is that Parkinson's may be a protein-folding neurological disorder like Alzheimer's syndrome. Current research is focusing on a protein called alpha-synuclein that is present in nerve cells and theoretically "mis-folds," gumming up the works that help transmit the chemical called dopamine through the brain.

All of these advances have helped the institute expand almost exponentially. Langston and his colleagues moved to their 40,000-square-foot location on Morse Avenue in 1994. "When we got here, you could shoot a cannon through the hallways and not hit anything," he says. "Now, we're bursting at the seams." Nearby condominium construction is threatening to crowd them out. Developers have razed vacant office parks and have come to them, asking to do the same to the institute.

Langston says that Sunnyvale is a convenient location for his employees and his patients and that moving would set their research back for nearly a year. But space is becoming an issue, one they'll have to address in the next few months.

For now, the institute continues to operate in near-anonymity. Langston relates the tale of a Sunnyvale resident who called one of the oldest Parkinson's groups in New York, looking for assistance, and was surprised to hear of a world-class institution right in her own backyard.

The institute is starting to branch out a little more on a local level, however. The Longitude Expedition, headed by a man from Los Gatos, is a drive around the world to raise money for Parkinson's research. The group took off from the institute's parking lot last fall. Mobley also says Stanford and the institute are looking to solidify a formal relationship in the next few months to help facilitate the exchange of resources and research. The institute is one of a few research institutions that is not linked to a college or university.

And if the legislative calendar in Sacramento allows it, the institute may be getting to know the rest of California much better as well. Assembly Bill 2248, which at press time was still in subcommittee, proposes a statewide registry for Parkinson's patients, a resource that could greatly help the institute's epidemiological efforts. "California is a phenomenal place because of its diversity and geography," Langston says. "That is a huge amount of data. That could do more than any other single thing we've done."

If passed, the bill would allow for a pilot program in three to four counties, but the end of the legislative session is looming. Assemblywoman Sally Lieber was scheduled to come by the institute to examine their data, but only time will tell whether the bill will actually see the governor's desk.

"It's amazing, the things you have to do to do good science," Langston says.

He says that for the future, he'd like to expand the institute's offerings to serve the whole patient, including occupational therapy and outreach. Of the half-dozen patients whose heroin addictions led to the institute's creation, several have died, another is in jail and just one is capable of fully taking care of herself.

When it comes to a cure, a cause and care, there's still a long way to go.