Parkinson's Disease a Mystery
A doctor's diagnosis can land like a punch in the solar plexus: you have Parkinson's disease. Chronic, progressive and incurable. In the life-altering reverberations that follow come the questions. Why? And in Don Williams's case, why did three people he worked with also get it? There are no answers, only theories. Williams, his one-time colleague Sally Gardner, and an anonymous cameraman were part of the same production unit at CBC Television in Vancouver in the late 1970s; all worked with Michael J. FOX before he became a star; all four are now losing control of their bodies to a cruel, dehumanizing disease. Why? Williams, 64, directed Fox in an episode of a short-lived sitcom called Nellie, Daniel, Emma and Ben, which aired in 1979. It was Fox's second gig, after his debut in the CBC comedy Leo and Me. Today, Williams is able to joke about his debilitating affliction. "I often say it's because when Michael J. and I worked together, we had to work with terrible scripts - it destroyed our brain cells."
It's funny and yet it's not. Parkinson's announced its unwelcome arrival with a tremor in Williams's right hand and forearm nine years ago. The former executive producer of the CBC TV hit series The Beachcombers, who also played a character called the Elder on The X-Files for four seasons, says fatigue now makes directing increasingly difficult. As an actor, he says, "I've been reduced to playing old men with serious ailments." No one has calculated the odds of four CBC employees getting Parkinson's. The cluster, however, raises the possibility that the cause is environmental - perhaps a virus or toxin. "I've been asked if I remember any unusual illnesses, flu or even a lot of colds or anything," says Williams. "I can't remember anything significant at all." The cluster has Fox wondering, too. "It could be a sick building, it could be that we were all in a park on a certain day, it could be coincidence," he says. "I don't know."
British physician James Parkinson first described the disease in 1817, calling it "the shaking palsy." It was only in the 1960s that researchers linked Parkinson's to dying nerve cells in the substantia nigra, a dark mass of cells in the mid-brain that produces dopamine, a chemical that allows nerves to communicate with each other for muscle control. There are several forms, collectively known as Parkinsonisms. The disease usually strikes people in their 50s and 60s, though up to 10 per cent of patients are diagnosed before turning 40. Nearly 100,000 Canadians have it.
For the most part, Parkinson's does not appear to be inherited, although a mutation in either of two genes can lead to the disease in rare cases. The condition causes tremors or shaking, muscle stiffness, an inability to move quickly and loss of coordination. Toward the end, its victims can't walk, their voices weaken, and swallowing becomes difficult. They live almost as long as they would have without the disease, but eventually they can do little more than stare blankly ahead.
Depression, sleep disturbances, constipation - the list of secondary effects is long. About one-quarter of patients are struck by dementia. As for its causes, Parkinson's, like some other conditions, could have several, says Dr. Donald Calne, a former director of Vancouver's Pacific Parkinson's Research Centre. Pneumonia, for instance, can result from viruses or bacteria; genetics, viruses or exposure to some chemicals may produce cancer. "Our understanding of Parkinson's," says Calne, "is where we were with pneumonia 200 years ago."
Medical progress has been slow. The best treatment - taking the drug L-dopa to help the brain synthesize dopamine - is more than 30 years old. While L-dopa lessens symptoms, it can also cause nausea and hallucinations, says Dr. Ali Rajput, chairman of the scientific advisory committee for Parkinson Society Canada. Prolonged use can reduce its effectiveness and induce writhing. "The patients' quality of life improves and they live longer," says Rajput, "but it's not a cure."
More invasive alternatives have been tried, with varying success. Implanting fetal brain cells in the patient's brain has shown encouraging results, but the controversial treatment remains experimental. Implanted retinal cells, which for reasons unknown produce dopamine, also show promise. Scientists hope one day to implant embryonic stem cells with the ability to grow into brain cells. Some patients opt for a pallidotomy - a surgeon destroys cells in part of the brain called the globus pallidus, interrupting a neural pathway to decrease symptoms, including writhing, tremors and rigidity. Researchers have also inserted electrical probes deep into the brain to quell tremors. Others continue tests with drugs that protect dopamine-producing cells, but none have made it to market.
Attempts at solving the Parkinson's mystery have yielded tantalizing clues. After the First World War, millions of people worldwide contracted encephalitis lethargica, or a type of sleeping sickness, before the disease strangely disappeared in the 1920s. A third of them died. Then, several years after the acute phase of the viral disease passed, many of the survivors succumbed to a condition with symptoms similar to those of Parkinson's, known as postencephalitic Parkinsonism. A group of those patients in New York, some in a catatonic state, were the subject of the book Awakenings by Dr. Oliver Sacks, later made into a movie. In 1969, Sacks gave these patients L-dopa, a new drug at the time. Their subsequent physical "awakening" was remarkable but short lived. Still, it underscored L-dopa's therapeutic effectiveness and, given the sleeping sickness connection, linked Parkinson's to viral infection.
People in close contact with others - health-care professionals, miners, teachers, forestry workers who bunk together - appear to be twice as likely as the general population to get Parkinson's. These findings, taken together with the occasional appearance of clusters like the Vancouver one, suggest viruses or toxins are to blame, says Calne. He doesn't see Parkinson's as a disease that slowly destroys brain cells. Rather, he suspects that a brief event - a viral infection, perhaps, or exposure to a powerful toxin - has damaged dopamine-producing cells. These "wounded" cells then die slowly over time. "Whatever the cause was," says Calne, "it's done the damage and gone."
There is powerful evidence of toxins playing an important role. In the early 1980s in California, a bad batch of synthetic heroin turned up on the streets of Silicon Valley. The junk was tainted with MPTP, or methyl-phenyl-tetrahydropyridine, a toxic chemical. Once injected, it damaged the substantia nigra, reducing the drug user to a catatonic state. Today, researchers are investigating the possibility of a link between Parkinson's and two common agents that are chemically similar to MPTP - the herbicide paraquat and the pesticide rotenone. Parkinson Society Canada notes that, for reasons unknown, the disease is more common in rural areas of industrialized countries, and in industrialized areas of rural countries.
Many aspects of Parkinson's remain unexplained. Research continues to shed new light, says Rajput, and "we are in a whole lot better shape today than we were 40 years ago." Unfortunately, indications that unknown agents in our environment may be destroying people's brains are far from reassuring.
See also DISEASE.
Maclean's April 29, 2002